zithromax and Asthma

Poorly controlled asthma is especially common in low resource countries. Aside from lack of access to, or poor technique with, inhaled beta-2 agonists and corticosteroids, the most problematic forms of asthma are frequently associated with both fungal allergy and exposure, especially in adults leading to more asthma exacerbations and worse asthma. The umbrella term 'fungal asthma' describes many disorders linked to fungal exposure and/or allergy to fungi. One fungal asthma endotype, ABPA, is usually marked by a very high IgE and its differential diagnosis is reviewed. Both ABPA and fungal bronchitis in bronchiectasis are marked by thick excess airway mucus production. Dermatophyte skin infection can worsen asthma and eradication of the skin infection improves asthma. Exposure to fungi in the workplace, home and schools, often in damp or water-damaged buildings worsens asthma, and remediation improves symptom control and reduces exacerbations. Antifungal therapy is beneficial for fungal asthma as demonstrated in nine of 13 randomised controlled studies, reducing symptoms, corticosteroid need and exacerbations while improving lung function. Other useful therapies include azithromycin and some biologics approved for the treatment of severe asthma. If all individuals with poorly controlled and severe asthma could be 'relieved' of their fungal allergy and infection through antifungal therapy without systemic corticosteroids, the health benefits would be enormous and relatively inexpensive, improving the long term health of over 20 million adults and many children. Antifungal therapy carries some toxicity, drug interactions and triazole resistance risks, and data are incomplete. Here we summarise what is known and what remains uncertain about this complex topic.

Topics: Adrenal Cortex Hormones; Adult; Antifungal Agents; Asthma; Azithromycin; Bronchiectasis; Child; Humans

Azithromycin (AZI) is increasingly used for childhood asthma despite limited and inconsistent data. We aimed to evaluate the efficacy and safety of AZI in childhood asthma.. We searched seven databases to include randomized controlled trials (RCTs) of AZI in the treatment of childhood asthma. Four reviewers independently screened the records. Risk of Bias 2 was used to assess the quality of RCTs. Risk ratios with 95% confidence interval (CI) from dichotomous outcomes, and mean difference (MD) with 95% CI from continuous outcomes were pooled.. AZI may be beneficial in improving some clinical symptoms and lung functions in older asthma children (over 6 years old) with persistent asthma. But it still requires further research.

Topics: Adolescent; Aged; Anti-Asthmatic Agents; Asthma; Azithromycin; Budesonide; Child; Disease Progression; Forced Expiratory Volume; Humans

Macrolides are antibiotics with antiviral, anti-inflammatory and immunomodulatory effects in together with their bacteriostatic effects. In addition to its beneficial effects on chronic respiratory diseases such as COPD, cystic fibrosis, diffuse panbronchiolitis, and bronchiectasis, its effects on uncontrolled severe asthma and asthma exacerbations have been the subject of research in recent years. In randomized controlled trials, azithromycin, a macrolide, has been shown to reduce asthma exacerbations and significantly improve asthma-related quality of life in both eosinophilic and non-eosinophilic asthma phenotypes. However, there are also differences such as doses, durations and some studies not showing its effectiveness in severe eosinophilic asthma. In the GINA report, azithromycin can be recommended as an add-on therapy in patients with uncontrolled non-T2 severe asthma despite high-dose inhaled corticosteroid/ long-acting beta2-agonist/long-acting antimuscariniric treatments, or in T2 severe asthma patients whose asthma is not under control despite biologic therapy. In this review, the use of macrolides, especially azithromycin, in the treatment of asthma, immunomodulatory activities and safety profiles are discussed on the basis of current studies and guidelines.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans; Macrolides; Quality of Life

Add-on azithromycin (AZM) significantly reduces exacerbations in poorly controlled asthma irrespective of disease phenotype. In a predefined substudy of the original AMAZES protocol (500 mg, three times a week for 48 weeks), we report that AZM treatment reduces key sputum inflammatory proteins (interleukin (IL)-6, IL-1β and extracellular DNA), which is more evident in non-eosinophilic asthma (NEA). Moreover, AZM reduced

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Cytokines; Humans; Prospective Studies; Sputum

The first clinical indication of non-antibiotic benefits of macrolides was in the Far East, in adults with diffuse panbronchiolitis. This condition is characterised by chronic airway infection, often with Pseudomonas aeruginosa, airway inflammation, bronchiectasis and a high mortality. Low dose erythromycin, and subsequently other macrolides, led in many cases to complete remission of the condition, and abrogated the neutrophilic airway inflammation characteristic of the disease. This dramatic finding sparked a flurry of interest in the many hundreds of macrolides in nature, especially their anti-inflammatory and immunomodulatory effects. The biggest subsequent trials of azithromycin were in cystic fibrosis, which has obvious similarities to diffuse panbronchiolitis. There were unquestionable improvements in lung function and pulmonary exacerbations, but compared to diffuse panbronchiolitis, the results were disappointing. Case reports, case series and some randomised controlled trials followed in other conditions. Three trials of azithromycin in preschool wheeze gave contradictory results; a trial in pauci-inflammatory adult asthma, and a trial in non-cystic fibrosis bronchiectasis both showed a significant reduction in exacerbations, but none matched the dramatic results in diffuse panbronchiolitis. There is clearly a huge risk of antibacterial resistance if macrolides are used widely and uncritically in the community. In summary, Azithromycin is not the answer to anything in paediatric respiratory medicine; the paediatric respiratory community needs to refocus on the dramatic benefits of macrolides in diffuse panbronchiolitis, use modern - omics technologies to determine the endotypes of inflammatory diseases and discover in nature or synthesise designer macrolides to replicate the diffuse panbronchiolitis results. We must now find out how to do better!

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiectasis; Bronchiolitis; Bronchiolitis Obliterans; Bronchiolitis, Viral; Child; Child, Preschool; Ciliary Motility Disorders; Cystic Fibrosis; Disease Progression; Drug Resistance, Bacterial; Haemophilus Infections; Humans; Infant; Lung Diseases, Interstitial; Lung Transplantation; Macrolides; Respiratory Sounds; Stem Cell Transplantation

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Azithromycin; Humans; Magnesium Sulfate; Nebulizers and Vaporizers

The aim of this manuscript is to outline an approach to severe asthma, which is among the most challenging problems faced by paediatric pulmonologists. A logical, protocolised approach is essential. The first step is to rule out alternative diagnoses. The next step is a multidisciplinary assessment. Severe, therapy resistant asthma (STRA) is rare, and most of those referred will improve if basic management is corrected, especially adherence to treatment. However some are unable or unwilling to make necessary changes (refractory asthma plus or refractory difficult asthma). Some, especially asthma in the obese, and those thought to have STRA, progress to bronchoscopic airway phenotyping and a parenteral steroid trial to determine an individualised treatment plan. Those with persistent eosinophilc airway inflammation should be considered for omalizumab, and mepolizumab. Pauci-inflammatory asthma remains a therapeutic challenge, with a paucity of evidence; increasing steroid therapy seems neither logical nor efficacious, but options include tiotropium and azithromycin. However the most important message to the paediatrician looking after a child with apprently severe asthma is that the answer is not uncritically escalating treatment, but finding the answer to the question, what is it about this child, and his/her environment, which means there is no response to what should be easily treated airway pathology? The answer usually requires input from a skilled and experienced multi-disciplinary team, without which management is unlikely to be succesful. CONCLUSION: When managing a child with severe asthma, a detailed multi-disciplinary is essential to get the basic management right, before prescribing biologicals.

Topics: Algorithms; Allergens; Anti-Asthmatic Agents; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Asthma; Asthma, Exercise-Induced; Azithromycin; Bronchodilator Agents; Bronchoscopy; Child; Comorbidity; Environmental Exposure; Eosinophilia; Glucocorticoids; Humans; Medication Adherence; Obesity; Omalizumab; Patient Care Team; Severity of Illness Index; Smoking; Tiotropium Bromide; Tobacco Smoke Pollution

Preventing exacerbations is an important goal of asthma treatment. Long-term treatment with azithromycin may help achieve this. Our aim was to conduct a systematic review and individual participant data (IPD) meta-analysis to examine the efficacy of azithromycin in reducing exacerbations in asthma, and in the subphenotypes of noneosinophilic asthma, eosinophilic asthma and severe asthma.. We completed a systematic search of Embase, MEDLINE, PubMed, Cochrane Library, ClinicalTrials.gov and reference lists of previous systematic reviews in February 2019. We included parallel-group, double-blind, randomised controlled trials in adults comparing at least 8 weeks of azithromycin treatment with placebo, where the outcome of exacerbations was assessed over at least 6 months. Data were extracted from published sources, Cochrane Risk of Bias Tool was applied and IPD were sought from authors. Reviews were undertaken in duplicate. We conducted an IPD meta-analysis on the primary outcome of exacerbations and a random effects meta-analysis for secondary outcomes.. Three studies were identified (n=604). In the IPD meta-analysis, treatment with azithromycin was associated with a reduced rate of exacerbations (oral corticosteroid course due to worsening asthma, antibiotic use for lower respiratory tract infection, hospitalisation and/or emergency department visits) in asthma as well as in the noneosinophilic, eosinophilic and severe asthma subgroups. Examining each exacerbation type separately, patients with eosinophilic asthma reported fewer oral corticosteroid courses, and patients with noneosinophilic and severe asthma reported fewer antibiotic courses. Azithromycin was well tolerated.. Maintenance use of azithromycin reduces exacerbations in patients with eosinophilic, noneosinophilic and severe asthma.

Topics: Asthma; Azithromycin; Disease Progression; Humans; Randomized Controlled Trials as Topic; Treatment Outcome

Effects of azithromycin on asthma reported in clinical trials are less consistent. We aimed to further clarify the efficacy and safety of azithromycin in treatment of asthma.. The protocol registration number was CRD42017074318 (http://www.crd.york.ac.uk/Prospero). We searched PubMed, EMBASE, Cochrane databases, China National Knowledge Internet (CNKI), and Wanfang databases for the randomized controlled trials (RCTs) with prolonged treatment of azithromycin for more than 3 weeks. Random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference (MD) for dichotomous and continuous data respectively.. A total of eight studies were included for analysis. The pooled result of adjunctive azithromycin therapy in asthma showed a small, but statistically significant increase in forced expiratory volume in one second (FEV1) (MD = 0.06, 95% confidence interval [CI]: 0.01-0.12, P = .02), but no significant differences in exacerbation frequency (MD = -0.42, 95%CI: -1.13 to 0.30, P = .25) and peak expiratory flow (PEF) (MD = 0.20, 95% CI: -0.05 to 0.44, P = .12), fractional exhaled nitric oxide (FeNO) (MD = 4.12, 95% CI: -2.06 to 10.30, P = .19), asthma quality of life questionnaire (AQLQ) (MD: 0.05, 95% CI: -0.17 to 0.28, P = .65), asthma control questionnaire (ACQ) (MD: -0.03, 95% CI: -0.21 to 0.15, P = .75). The subgroup analysis revealed that azithromycin could decrease FeNO among Asian asthma (MD = 15.04, 95% CI: 6.18-23.90, P = .0009).. Add-on therapy of azithromycin in asthma patients could improve the FEV1, but failed to improve asthma exacerbations, PEF, ACQ, AQLQ, and FeNO. Subgroup analysis indicated that azithromycin could improve FeNO in Asian group asthmatics.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans; Treatment Outcome

Azithromycin is a potential therapeutic choice for asthma control, which is a heterogeneous airway inflammatory disease. Because of variable findings, we intend to evaluate the therapeutic effect and safety of azithromycin in asthma. Databases, including PubMed, EMBASE, Cochrane, and CNKI until 31 December 2017, were searched to identify available randomised controlled trials regarding azithromycin treatment for asthma. We identified seven studies involving 1520 cases that met our criteria. The mean difference for lung function (FEV

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans; Prognosis; Quality of Life

Asthma is a heterogeneous disorder described by a large number of clinical features. A growing body of literature on more specific asthma phenotypes provides evidence for a phenotype-based approach to management in which specific therapies are recommended based on patient and disease characteristics. This understanding, coupled with an increase in the number of available therapies for children with asthma, as well as emerging therapies and phenotypic markers, will allow for improved asthma management in the future.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Asthma; Azithromycin; Biomarkers; Bronchial Thermoplasty; Child; Child, Preschool; Combined Modality Therapy; Eosinophils; Humans; Macrolides; Precision Medicine; Sputum

In chronic persistent asthma and severe acute exacerbations of bronchial asthma, infectious agents are the predominant triggers that drive disease and airway pathobiology. In acute exacerbations of bronchial asthma (AEBA) including near fatal and fatal asthma, viral agents, particularly human rhinovirus-C, respiratory syncytial virus and influenza A appear to be the more prevalent and recurring threats. Both viral, and to a lesser extent bacterial agents, can play a role, and co-infection may also be present and worsen prognosis in hospitalized patients, placing a portion at risk for critical asthma syndrome. During severe acute exacerbations, infectious agents must be treated empirically, but the initial treatment regimens can vary and viral coverage may also vary based on seasonality and patient age. Early treatment with ceftriaxone and azithromycin, along with oseltamivir in winter months, should be initiated with all cases of severe exacerbations where infection is suspected, and definitely in critical asthma syndrome until infection is excluded by appropriate diagnostic testing. In this manuscript we will outline the impact of the major viral agents on severe asthma including the data from the 2009 H1N1 influenza pandemic. The role of bacterial infections in acute exacerbations of asthma will also be reviewed as well as the benefit of empiric antibiotics and the role of macrolides in both acute and chronic asthma.

Topics: Animals; Asthma; Azithromycin; Bacterial Infections; Ceftriaxone; Coinfection; Critical Illness; Disease Progression; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Oseltamivir; Seasons; Syndrome

To evaluate the effectiveness and safety of azithromycin in treatment of bronchial asthma.. Reports of randomized controlled trials (RCTs) describing azithromycin for treatment of asthma published before December 2013 were searched in CNKI, WANFANG, PubMed and Medline databases. The data of the included RCTs were extracted and the data quality was evaluated by two assessors independently. Meta-analyses were performed with Revman 5.1 software.. Eight RCTs were identified. Meta-analysis of the data showed that compared with the control group, azithromycin treatment significantly improved the patients' PEF (WMD=0.15, 95%CI=0.06-0.24, P=0.001), scores of asthma control test (ACT) (WMD=1.59, 95%CI=0.95-2.23, P<0.00001), and FEV1% (WMD=1.44, 95%CI=0.40-2.49, P=0.007), but the improvement of FEV1% was observed only in Chinese patients (WMD=1.48, 95%CI=0.40-2.57, P=0.007). The scores of asthma control questionnaire (WMD=0.07, 95%CI=-0.11-0.25, P=0.45) or asthma quality of life questionnaire (WMD=-0.06, 95%CI=-0.42-0.31, P=0.77) were not affected by azithromycin. No severe adverse events were reported in these included studies.. Azithromycin for asthma treatment can improve PEF, ACT and FEV1% (in Chinese patients only) but shows no significant effect on the quality of life of the patients. Azithromycin is well tolerated and may therefore be beneficial as adjuvant therapy for asthma.

Topics: Asthma; Azithromycin; Humans; Quality of Life; Randomized Controlled Trials as Topic

Increasing understanding of mechanisms and influencing factors in the development of uncontrolled inflammatory responses in atopy and asthma should serve for the introduction of new preventive measures. This review tries to present the current state of the art and resumes that until now, no really effective concept can be offered to families at risk.. In addition to modified feeding regimes (hydrolysed formula feeding in infancy), timing of the introduction of solids (avoidance of allergens versus early induction of tolerance), immune modulation using prebiotics or probiotics, a new target of potential intervention could be the human microbiome as a key player in the development of inflammatory diseases such as allergy and asthma. However, during the last 5 years, this concept could not yet be verified in interventional trials. There are new trials ongoing, studying the effect of microbial compounds in early infancy, vitamin D and polyunsaturated fatty acid supplementation during late pregnancy and the effect of azithromycin in children with recurrent wheeze. Results are to be expected within the next couple of years.. New data on multifaceted intervention and the analysis of the human microbiome are to be expected. The recommendation for atopy and asthma prevention still focuses on avoidance of tobacco smoke exposure and food allergens during the first 4 months of life and feeding of hydrolysed formula if breast-feeding is not possible in high-risk infants, potentially early feeding of prebiotic sugars and/or certain strains of probiotic bacteria or bacterial compounds in certain subpopulations.

Topics: Allergens; Anti-Bacterial Agents; Asthma; Azithromycin; Clinical Trials as Topic; Feeding Behavior; Genetic Predisposition to Disease; Humans; Hypersensitivity, Immediate; Immunomodulation; Infant; Metagenome; Probiotics; Vitamin D

Antibiotics have significant role in the treatment of respiratory diseases. The main aim of their use is to treat infection, but anti-inflammatory properties of macrolides are also beneficial in selected diseases. The role of antibiotics in the therapy of asthma exacerbation can be neglected and should be limited to exceptional situations of bacterial infections which are very rare. During last few years the role of atypical infections in asthma inception, induction of exacerbation and modification of chronic course of disease has been discussed. Antibiotics play significant role in cystic fibrosis therapy. They are especially recommended during exacerbation, when new pathogens are revealed and in chronic Pseudomonas aeruginosa infection. This paper includes the principal rules of antibiotics therapy in patients with cystic fibrosis. The role of azithromycin in antiinflammatory therapy in this group of patients is also presented.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Asthma; Azithromycin; Child; Cystic Fibrosis; Humans; Respiratory Tract Infections

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide. The Global Burden of Disease study has concluded that COPD will become the third leading cause of death worldwide by 2020, and will increase its ranking of disability-adjusted life years lost from 12th to 5th. Acute exacerbations of COPD (AECOPD) are associated with impaired quality of life and pulmonary function. More frequent or severe AECOPDs have been associated with especially markedly impaired quality of life and a greater longitudinal loss of pulmonary function. COPD and AECOPDs are characterized by an augmented inflammatory response. Macrolide antibiotics are macrocyclical lactones that provide adequate coverage for the most frequently identified pathogens in AECOPD and have been generally included in published guidelines for AECOPD management. In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors. Macrolide antibiotics have been used to successfully treat a number of chronic, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis. Data in COPD patients have been limited and contradictory but the majority hint to a potential clinical and biological effect. Additional, prospective, controlled data are required to define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiectasis; Bronchiolitis; Cystic Fibrosis; Disease Progression; Humans; Macrolides; Pulmonary Disease, Chronic Obstructive; Quality of Life

Topics: Anti-Infective Agents; Asthma; Azithromycin; Bronchiolitis; Chronic Disease; Clinical Trials as Topic; Cystic Fibrosis; Erythromycin; Gene Expression Regulation, Bacterial; Humans; Macrolides; Mucins; Neutrophils; Pancreatic Elastase; Pseudomonas aeruginosa; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Sinusitis; Structure-Activity Relationship

For more than 20 years macrolide antibiotics have been used to treat chronic inflammatory airway diseases based on their immunomodulatory activity. Macrolide antibiotics down-regulate damaging prolonged inflammation as well as increase mucus clearance, decrease bacterial virulence and prevent biofilm formation. Initially shown to decrease morbidity and mortality in diffuse panbronchiolitis and in steroid-dependent asthma, long-term macrolide therapy has now been shown to significantly reduce exacerbations and improve lung function and quality of life in children with cystic fibrosis. They have also proven beneficial in Japanese children and adults with chronic sinobronchitis especially when there is nasal polyposis. Long-term macrolides have also proven clinically beneficial in some patients with plastic bronchitis. Adverse reactions are few and generally self-limited when used at the recommended dosage for immunomodulation.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Bronchitis; Child; Clarithromycin; Cystic Fibrosis; Drug Resistance; Humans; Inflammation; Macrolides; Respiratory Tract Diseases

To investigate the efficacy and adverse reactions of methylprednisolone plus azithromycin in the treatment of children with refractory mycoplasma pneumoniae pneumonia (RMPP) and its effect on fractional exhaled nitric oxide (FeNO) and peripheral blood eosinophils (EOS).. Comparative study.. Daqing Oilfield General Hospital, China, from June 2019 to January 2021.. A total of 102 children with RMPP were randomly divided into Group A (n = 51) and Group B (n = 51) by the random number table. Group A was treated with azithromycin alone, and Group B was treated with methylprednisolone plus azithromycin. The efficacy, adverse reactions, FeNO and EOS levels were compared.. The total effective rate of treatment in Group B was higher than that in Group A (p=0.006). Time of cough disappearance, lung shadow disappearance, defervescence and hospitalisation in Group B was shorter than that in Group A (p=0.033, 0.008, 0.004 and <0.001, respectively). After treatment, the FeNO and EOS levels in Group B were lower than those in Group A (both p <0.001).. The efficacy of methylprednisolone plus azithromycin in treatment of RMPP is better than azithromycin alone. The former can reduce the levels of FeNO and EOS more effectively than the latter. Key Words: Refractory mycoplasma pneumoniae pneumonia (RMPP), Methylprednisolone, Azithromycin, Fractional exhaled nitric oxide (FeNO), Eosinophils (EOS).

Topics: Asthma; Azithromycin; Child; Eosinophils; Fractional Exhaled Nitric Oxide Testing; Humans; Methylprednisolone; Mycoplasma pneumoniae; Nitric Oxide; Pneumonia, Mycoplasma

Steroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease. Macrolide add-on therapy can improve the quality of life and the exacerbation rate in refractory cases, possibly with greater effectiveness in neutrophilic phenotypes. The mechanisms leading to these beneficial effects are incompletely understood and whether macrolides potentiate the modulation of bronchial remodeling induced by inhaled corticosteroids (ICS) is unknown. The objective of this study was to determine if adding azithromycin to ICS leads to further improvement of lung function, airway inflammation and bronchial remodeling in severe asthma. The combination of azithromycin (10 mg/kg q48h PO) and inhaled fluticasone (2500 µg q12h) was compared to the sole administration of fluticasone for five months in a randomized blind trial where the lung function, airway inflammation and bronchial remodeling (histomorphometry of central and peripheral airways and endobronchial ultrasound) of horses with severe neutrophilic asthma were assessed. Although the proportional reduction of airway neutrophilia was significantly larger in the group receiving azithromycin, the lung function and the peripheral and central airway smooth muscle mass decreased similarly in both groups. Despite a better control of airway neutrophilia, azithromycin did not potentiate the other clinical effects of fluticasone.

Topics: Administration, Inhalation; Airway Remodeling; Animals; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchodilator Agents; Drug Therapy, Combination; Female; Fluticasone; Horse Diseases; Horses; Male; Neutrophils

Azithromycin has immunomodulatory actions, and its beneficial effects have been demonstrated in asthmatic adults. Data on children are limited.. Does the addition of oral azithromycin to standard therapy in children with poorly controlled asthma improve asthma control compared with standard treatment alone?. This open-label randomized controlled trial included children (5-15 years of age) with poorly controlled asthma defined by Asthma Control Test (ACT) and Childhood Asthma Control Test (CACT) score of ≤ 19. They were randomized to receive azithromycin (10 mg/kg) three times weekly for 3 months along with standard treatment or standard treatment alone. The primary outcome was the ACT and CACT scores at 3 months. Secondary outcomes were asthma control according to Global Initiative for Asthma (GINA) guidelines, the number of exacerbations, change in spirometry parameters, change in fractional exhaled nitric oxide (Feno) level, positive throat swab results, and side effects.. The trial included 120 children (89 boys; 60 in each group). The mean ± SD age was 9.9 ± 3 years. The baseline parameters were similar between the groups. Mean ± SD ACT and CACT scores (available for 115 children) at 3 months of intervention were 21.71 ± 2.17 vs 18.33 ± 2.19 (P < .001) in the azithromycin and control groups, respectively. The numbers of children with well-controlled asthma according to GINA guidelines were 41 of 56 vs 10 of 56 in the azithromycin and control groups, respectively (P < .001). The median number of exacerbations requiring emergency visit and steroid use were fewer in the azithromycin group: 0 (interquartile range [IQR], 3) vs 1 [IQR, 6]; P < .001). No difference was found in Feno level, spirometry parameters, positive throat swab results, and adverse effects between the groups.. The use of azithromycin in children with poorly controlled asthma resulted in improved asthma control and reduced exacerbations.. Clinical Trials Registry - India; No.: CTRI/2019/06/019727; URL: www.ctri.nic.in.

Topics: Adult; Asthma; Azithromycin; Child; Humans; India; Male; Nitric Oxide; Spirometry

Previous randomised controlled trials (RCTs) suggest antibiotics for treating episodes of asthma-like symptoms in preschool children. Further, high-dose vitamin D supplementation has been shown to reduce the rate of asthma exacerbations among adults with asthma, while RCTs in preschool children are lacking. The aims of this combined RCT are to evaluate treatment effect of azithromycin on episode duration and the preventive effect of high-dose vitamin D supplementation on subsequent episodes of asthma-like symptoms among hospitalised preschoolers.. Eligible participants, 1-5 years old children with a history of recurrent asthma-like symptoms hospitalised due to an acute episode, will be randomly allocated 1:1 to azithromycin (10 mg/kg/day) or placebo for 3 days (n=250). Further, independent of the azithromycin intervention participants will be randomly allocated 1:1 to high-dose vitamin D (2000 IU/day+ standard dose 400 IU/day) or standard dose (400 IU/day) for 1 year (n=320). Participants are monitored with electronic diaries for asthma-like symptoms, asthma medication, adverse events and sick-leave. The primary outcome for the azithromycin intervention is duration of asthma-like symptoms after treatment. Secondary outcomes include duration of hospitalisation and antiasthmatic treatment. The primary outcome for the vitamin D intervention is the number of exacerbations during the treatment period. Secondary outcomes include time to first exacerbation, symptom burden, asthma medication and safety.. The RCTs are approved by the Danish local ethical committee and conducted in accordance with the guiding principles of the Declaration of Helsinki. The Danish Medicines Agency has approved the azithromycin RCT, which is monitored by the local Unit for Good Clinical Practice. The vitamin D RCT has been reviewed and is not considered a medical intervention. Results will be published in peer-reviewed journals and presented at international conferences.. NCT05028153, NCT05043116.

Topics: Asthma; Azithromycin; Child, Preschool; Double-Blind Method; Humans; Infant; Randomized Controlled Trials as Topic; Vitamin D; Vitamins

Asthma-like symptoms in young children are orchestrated by the local airway immune response, but current knowledge largely relies on in vitro airway models. Azithromycin has been shown to reduce the duration of episodes with asthma-like symptoms, but efficacy may depend on the individual child's immune response.. To investigate in vivo upper airway immune mediator levels during episodes with asthma-like symptoms in young children and their ability to predict the clinical response to azithromycin treatment.. A total of 535 children aged 0-3 years from the Copenhagen Prospective Studies of Asthma in Childhood-2010 mother-child cohort were examined for immune mediator levels in samples of nasal epithelial lining fluid during episodes with asthma-like symptoms as well as in the asymptomatic state. In a sub-study, children with recurrent asthma-like symptoms were randomized to either a 3-day course of oral azithromycin (10 mg/kg; n = 32) or placebo (n = 38). In the current study, we compared the pretreatment immune mediator levels with the clinical response to treatment with azithromycin in an exploratory post hoc analysis.. The immune mediator concentrations during vs outside episodes were significantly upregulated for IFN-ɣ (ratio 1.73), TNF-α (ratio 2.05), IL-1β (ratio 1.45), IL-10 (ratio 1.97), while CCL22 (ratio 0.65) was downregulated. Low levels of TNF-α and IL-10 and high levels of CCL22 predicted better treatment response to azithromycin (P-values < .05).. Upper airway immune mediator levels were altered during episodes of asthma-like symptoms, and levels of TNF-α, CCL22, and IL-10 may predict the response to azithromycin treatment.

Topics: Asthma; Azithromycin; Child; Child, Preschool; Cohort Studies; Humans; Prospective Studies

The AMAZES randomized controlled trial demonstrated that long-term low-dose azithromycin treatment reduces exacerbations of poorly controlled asthma, but the therapeutic mechanisms remain unclear. Dysregulation of the inflammatory tumour necrosis factor (TNF) pathway is implicated in asthma and could be suppressed by azithromycin. We aimed to determine the inflammatory and clinical associations of soluble TNF signalling proteins (TNF receptors [TNFR] 1 and 2, TNF) in sputum and serum, and to test the effect of 48 weeks of azithromycin vs placebo on TNF markers.. Sputum supernatant and serum TNFR1, TNFR2 (n = 142; 75 azithromycin-treated, 67 placebo-treated) and TNF (n = 48; 22 azithromycin-treated, 26 placebo-treated) were measured by ELISA in an AMAZES trial sub-population at baseline and end of treatment. Baseline levels were compared between sputum inflammatory phenotypes, severe/non-severe asthma and frequent/non-frequent exacerbators. Effect of azithromycin on markers was tested using linear mixed models.. Baseline sputum TNFR1 and TNFR2 were significantly increased in neutrophilic vs non-neutrophilic asthma phenotypes, while serum markers did not differ. Sputum TNFR1 and TNFR2 were increased in severe asthma and correlated with poorer lung function, worse asthma control and increasing age. Serum TNFR1 was also increased in severe asthma. Sputum and serum TNFR2 were increased in frequent exacerbators. Azithromycin treatment significantly reduced sputum TNFR2 and TNF relative to placebo, specifically in non-eosinophilic participants.. We demonstrate dysregulation of TNF markers, particularly in the airways, that relates to clinically important phenotypes of asthma including neutrophilic and severe asthma. Suppression of dysregulated TNF signalling by azithromycin could contribute to its therapeutic mechanism.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Biomarkers; Humans; Sputum; Tumor Necrosis Factor-alpha

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Child, Preschool; Cohort Studies; Female; Humans; Infant; Male; Microbiota; Prospective Studies; Reinfection

Improved diagnostic tools for predicting future exacerbation frequency in asthmatic patients are required. A sputum gene expression signature of 6 biomarkers (6-gene signature [6GS], including Charcot-Leyden crystal galectin [CLC]; carboxypeptidase 3 [CPA3]; deoxyribonuclease 1-like 3 [DNASE1L3]; alkaline phosphatase, liver/bone/kidney [ALPL]; CXCR2; and IL1B) predicts inflammatory and treatment response phenotypes in patients with stable asthma. Recently, we demonstrated that azithromycin (AZM) add-on treatment in patients with uncontrolled moderate-to-severe asthma significantly reduced asthma exacerbations (AMAZES clinical trial).. We sought to test whether the 6GS predicts future exacerbation and inflammatory phenotypes in a subpopulation of AMAZES and to test the effect of AZM therapy on 6GS expression and prognostic capacity.. One hundred forty-two patients (73 placebo-treated and 69 AZM-treated patients) had sputum stored for quantitative PCR of 6GS markers at baseline and after 48 weeks of treatment. Logistic regression and receiver operating characteristic and area under the curve (AUC) determination were performed on baseline measures, and in an exploratory analysis the predictive value of the 6GS was compared with conventional biomarkers for exacerbation and inflammatory phenotypes.. The 6GS significantly predicted all future exacerbation phenotypes tested. Calculated AUCs for the 6GS were significantly greater than AUCs for peripheral blood eosinophil counts, sputum neutrophil counts, and combined sputum eosinophil and neutrophil counts. 6GS AUCs were also numerically but not significantly greater than those for fractional exhaled nitric oxide values and sputum eosinophil counts. AZM treatment altered neither 6GS expression nor the predictive capacity of the 6GS for future exacerbation phenotypes. The 6GS was a significant predictor of airway inflammatory phenotype in this population.. We demonstrate that a sputum gene signature can predict future exacerbation phenotypes of asthma, with the greatest biomarker performance in identifying those who would experience frequent severe exacerbations. AZM therapy did not modify 6GS expression or biomarker performance, suggesting the therapeutic action of AZM is independent of 6GS-related inflammatory pathways.

Topics: Aged; Anti-Bacterial Agents; Asthma; Azithromycin; Double-Blind Method; Eosinophils; Female; Humans; Leukocyte Count; Male; Middle Aged; Neutrophils; Phenotype; Severity of Illness Index; Sputum; Transcriptome

Topics: Adult; Aged; Anti-Bacterial Agents; Asthma; Azithromycin; Bacterial Load; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Haemophilus influenzae; Humans; Male; Middle Aged; Moraxella catarrhalis; Pseudomonas aeruginosa; Sputum; Staphylococcus aureus; Streptococcus pneumoniae

Neutrophilic inflammation is believed to contribute to the airway obstruction and remodelling in equine asthma. Azithromycin, an antibiotic with immunomodulatory properties, reduces pulmonary neutrophilia and hyper-responsiveness in human asthmatics and decreases airway remodelling in rodent models of asthma. It was therefore hypothesised that azithromycin would improve lung function, mucus accumulation and central airway remodelling by decreasing luminal neutrophilia in severe equine asthma. The effects of a 10-day treatment with either azithromycin or ceftiofur, an antimicrobial without immune-modulating activity, were assessed using a blind, randomised, crossover design with six severe asthmatic horses in clinical exacerbation. Lung function, tracheal mucus accumulation, tracheal wash bacteriology, bronchial remodelling, airway neutrophilia and mRNA expression of proinflammatory cytokines (interleukin (IL)-8, IL-17A, IL-1β, tumour necrosis factor-α) in bronchoalveolar lavage fluid were evaluated. Azithromycin decreased the expression of IL-8 (P=0.03, one-tailed) and IL-1β (P=0.047, one-tailed) but failed to improve the other variables evaluated. Ceftiofur had no effect on any parameter. The reduction of neutrophilic chemoattractants (IL-8, IL-1β) justifies further efforts to investigate the effects of a prolonged treatment with macrolides on airway neutrophilia and remodelling. The lack of efficacy of ceftiofur suggests that severe equine asthma should not be treated with antibiotics at first-line therapy.

Topics: Airway Remodeling; Animals; Asthma; Azithromycin; Cross-Over Studies; Female; Horse Diseases; Horses; Immunologic Factors; Inflammation; Lung; Male; Mucus; Respiratory Function Tests; Trachea

Cough variant asthma (CVA), as one of bronchitis diseases, features with repeated cough. In clinics, CAV does not show significant abnormal signs, therefore antibiotic therapy can hardly achieve satisfactory treatment effect. With the development of scientific technologies, the correlation between mycoplasma pneumoniae infection and CVA has become a hot research topic in clinics. In clinics, mycoplasma pneumoniae is extensively regarded as major cause for CVA, with complex pathogenic mechanism. The symptoms of CVA is characterized by chronic non abnormal inflammation, normally accompanied with bronchospasm and intestinal infection. Clinical practices show that about 6% of CVA children mainly show continuous cough till midnight during onset period, which is easily to misdiagnosed as bronchitis. Mycoplasma pneumoniae infection is a common disease threatening Children's health in China. With the annual increase of incidence of infantile pneumonia in China, mycoplasma pneumoniae infection has become a major reason leading to the death of child in China. More such mycoplasma pneumoniae infection is a sporadic disease spreading in a small range, and can onset in four seasons, making great impact on living quality and health of children. On this basis, this paper analyzes the correlation between Children's CVA and mycoplasma pneumoniae infection, in the hope of providing valuable reference for clinical treatment.

Topics: Adolescent; Asthma; Azithromycin; Child; Child, Preschool; China; Comorbidity; Cough; Erythromycin; Female; Humans; Immunoglobulin M; Incidence; Infant; Male; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Treatment Outcome

Exacerbations of asthma cause a substantial global illness burden. Adults with uncontrolled persistent asthma despite maintenance treatment require additional therapy. Since macrolide antibiotics can be used to treat persistent asthma, we aimed to assess the efficacy and safety of oral azithromycin as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high dose inhaled corticosteroids plus a long-acting bronchodilator.. We did a randomised, double-blind, placebo controlled parallel group trial to determine whether oral azithromycin decreases the frequency of asthma exacerbations in adults (≥18 years) with symptomatic asthma despite current use of inhaled corticosteroid and long-acting bronchodilator, and who had no hearing impairment or abnormal prolongation of the corrected QT interval. Patients were randomly assigned (1:1) to receive azithromycin 500 mg or placebo three times per week for 48 weeks. Patients were centrally allocated using concealed random allocation from a computer-generated random numbers table with permuted blocks of 4 or 6 and stratification for centre and past smoking. Primary efficacy endpoints were the rate of total (severe and moderate) asthma exacerbations over 48 weeks and asthma quality of life. Data were analysed on an intention-to-treat basis. The trial is registered at the Australian and New Zealand Clinical Trials Registry (ANZCTR), number 12609000197235.. Between June 12, 2009, and Jan 31, 2015, 420 patients were randomly assigned (213 in the azithromycin group and 207 in the placebo group). Azithromycin reduced asthma exacerbations (1·07 per patient-year [95% CI 0·85-1·29]) compared with placebo (1·86 per patient-year [1·54-2·18]; incidence rate ratio [IRR] 0·59 [95% CI 0·47-0·74]; p<0·0001). The proportion of patients experiencing at least one asthma exacerbation was reduced by azithromycin treatment (127 [61%] patients in the placebo group vs 94 [44%] patients in the azithromycin group, p<0·0001). Azithromycin significantly improved asthma-related quality of life (adjusted mean difference, 0·36 [95% CI 0·21-0·52]; p=0·001). Diarrhoea was more common in azithromycin-treated patients (72 [34%] vs 39 [19%]; p=0·001).. Adults with persistent symptomatic asthma experience fewer asthma exacerbations and improved quality of life when treated with oral azithromycin for 48 weeks. Azithromycin might be a useful add-on therapy in persistent asthma.. National Health and Medical Research Council of Australia, John Hunter Hospital Charitable Trust.

Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Aged; Analysis of Variance; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchodilator Agents; Double-Blind Method; Female; Humans; Male; Middle Aged; Quality of Life; Treatment Outcome; Young Adult

Antibiotics are frequently used to treat wheezing children. Macrolides may be effective in treating bronchiolitis and asthma.. We completed a prospective, double-blinded, randomized placebo-control trial of azithromycin among pre-school children (12 to 60 months of age) presenting to the emergency department with wheeze. Patients were randomized to receive either five days of azithromycin or placebo. Primary outcome was time to resolution of respiratory symptoms after treatment initiation. Secondary outcomes included the number of days children used a Short-Acting Beta-Agonists during the 21 day follow-up and time to disease exacerbation during the following six months (unscheduled health care visit or treatment with an oral corticosteroid for acute respiratory symptoms).. Of the 300 wheezing children recruited, 222 and 169 were analyzed for the primary and secondary outcomes, respectively. The treatment groups had similar demographics and clinical parameters at baseline. Median time to resolution of respiratory symptoms was four days for both treatment arms (interquartile range (IQR) 3,6; p = 0.28). Median number of days of Short-Acting Beta-Agonist use among those who received azithromycin was four and a half days (IQR 2, 7) and five days (IQR 2, 9; p = 0.22) among those who received placebo. Participants who received azithromycin had a 0.91 hazard ratio for time to six-month exacerbation compared to placebo (95% CI 0.61, 1.36, p = 0.65). A pre-determined subgroup analysis showed no differences in outcomes for children with their first or repeat episode of wheezing. There was no significant difference in the proportion of participants experiencing an adverse event.. Azithromycin neither reduced duration of respiratory symptoms nor time to respiratory exacerbation in the following six months after treatment among wheezing preschool children presenting to an emergency department. There was no significant effect among children with either first-time or prior wheezing.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Child, Preschool; Disease Progression; Double-Blind Method; Emergency Service, Hospital; Female; Humans; Infant; Male; Prognosis; Prospective Studies; Respiratory Sounds; Survival Rate

Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period.. In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1-3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476·20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verified by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297.. Between Nov 17, 2010, and Jan 28, 2014, we randomly allocated 158 asthma-like episodes in 72 children (79 [50%] to azithromycin and 79 [50%] to placebo). The mean duration of the episode after treatment was 3·4 days for children receiving azithromycin compared with 7·7 days for children receiving placebo. Azithromycin caused a significant shortening of the episode of 63·3% (95% CI 56·0-69·3; p<0·0001). The effect size increased with early initiation of treatment, showing a reduction in episode duration of 83% if treatment was initiated before day 6 of the episode compared with 36% if initiated on or after day 6 (p<0·0001). We noted no differences in clinical adverse events between the azithromycin (18 [23%] of 78 episodes included in final analysis) and placebo (24 [30%] of 79) groups (p=0·30), but we did not investigate bacterial resistance patterns after treatment.. Azithromycin reduced the duration of episodes of asthma-like symptoms in young children, suggesting that this drug could have a role in acute management of exacerbations. Further research is needed to disentangle the inflammatory versus antimicrobial aspects of this relation.. Lundbeck Foundation, Danish Ministry of Health, Danish Council for Strategic Research, Capital Region Research Foundation.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Anti-Bacterial Agents; Asthma; Azithromycin; C-Reactive Protein; Child, Preschool; Cough; Denmark; Double-Blind Method; Dyspnea; Early Medical Intervention; Female; Hospitalization; Humans; Infant; Male; Respiratory Sounds; Time Factors

Chronic cough is a common clinical problem worldwide. Although many patients have underlying precipitating conditions such as asthma, gastroesophageal reflux, or rhinitis, many remain symptomatic despite treating these conditions. New approaches are needed for the treatment of this group of patients.. We conducted a randomized, double-blind, placebo-controlled trial to determine whether 250 g of azithromycin three times a week for 8 weeks would affect the Leicester Cough Questionnaire (LCQ) score in 44 patients with treatment-resistant cough. Cough severity on a visual analog scale and bronchial exhaled nitric oxide were measured as secondary outcomes.. There was a clinically important improvement in LCQ score with azithromycin (mean change, 2.4; 95% CI, 0.5 to 4.2) but not placebo (mean change, 0.7; 95% CI, -0.6 to 1.9), but the between-group difference was not statistically significant (P = .12). There were no significant between-group differences for any of the secondary outcome measures. Looking at subgroups of responders, there was a large and significant improvement in LCQ score in patients with chronic cough and a concurrent diagnosis of asthma who were treated with azithromycin (mean, 6.19; 95% CI, 4.06 to 8.32).. Treatment with low-dose azithromycin for 8 weeks did not significantly improve LCQ score compared with placebo. The use of macrolides for treatment-resistant cough cannot be recommended from this study, but they may have a place in the treatment of chronic cough associated with asthma; this is worthy of further investigation.. WHO International Clinical Trials Registry; No.: ISRCTN75749391. URL: http://apps.who.int.

Topics: Aged; Anti-Bacterial Agents; Asthma; Azithromycin; Chronic Disease; Cough; Double-Blind Method; Female; Humans; Male; Middle Aged; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use.. To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit.. The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids.. Azithromycin 500 mg daily or matched placebo for 3 days.. The primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of -0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score.. Of 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference, -0.166; 95% CI, -0.670 to 0.337), nor on any day between exacerbation and day 10. No significant between-group differences were observed in quality-of-life questionnaires or lung function between exacerbation and day 10, or in time to 50% reduction in symptom score.. In this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics.. clinicaltrials.gov Identifier: NCT01444469.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Bacterial Infections; Disease Progression; Double-Blind Method; Emergency Medical Services; Female; Humans; Male; Middle Aged; Quality of Life; Treatment Outcome; United Kingdom

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Azithromycin; Double-Blind Method; Humans; Middle Aged; Smoking; Surveys and Questionnaires; Tobacco Use Disorder; Treatment Outcome; Young Adult

Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides.. We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ).. The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci.. Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. CLINICALTRIALS.GOV NUMBER: NCT00760838.

Topics: Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Treatment Outcome

Clinical trials in children with moderate-to-severe persistent asthma are limited.. We sought to determine whether azithromycin or montelukast are inhaled corticosteroid sparing.. The budesonide dose (with salmeterol [50 microg] twice daily) necessary to achieve control was determined in children 6 to 17 years of age with moderate-to-severe persistent asthma. After a budesonide-stable period of 6 weeks, children were randomized in a double-masked, parallel, multicenter study to receive once-nightly azithromycin, montelukast, or matching placebos plus the established controlling dose of budesonide (minimum, 400 microg twice daily) and salmeterol twice daily. Primary outcome was time from randomization to inadequate asthma control after sequential budesonide dose reduction.. Of 292 children screened, only 55 were randomized. Inadequate adherence to study medication (n = 80) and improved asthma control under close medical supervision (n = 49) were the major reasons for randomization failure. A futility analysis was requested by the Data Safety Monitoring Board. In data available for analyses, no differences were noted for either treatment compared with placebo in time to inadequate control status (median: azithromycin, 8.4 weeks [95% confidence limit, 4.3-17.3]; montelukast, 13.9 weeks [95% confidence limit, 4.7-20.6]; placebo, 19.1 weeks [95% confidence limit, 11.7-infinity]), with no difference between the groups (log-rank test, P = .49). The futility analysis indicated that even if the planned sample size was reached, the results of this negative study were unlikely to be different, and the trial was prematurely terminated.. Based on these results, neither azithromycin nor montelukast is likely to be an effective inhaled corticosteroid-sparing alternative in children with moderate-to-severe persistent asthma.

Topics: Acetates; Adolescent; Albuterol; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Medication Adherence; Quinolines; Salmeterol Xinafoate; Severity of Illness Index; Sulfides; Time Factors

Chlamydia pneumoniae is one of the most frequent pathogens causing airways infections. Contribution of chronic chlamydial infection to the following diseases: asthma, POChP, coronary heart disease, abdominal aortic aneurysm, is particularly interesting. The connection between such infection and bronchial asthma was described in the literature in 1991. C. pneumoniae often causes asthma exacerbation; it is suggested that it also may be an etiologic factor of the disease. In a group of 55 subjects with chronic, stable bronchial asthma treated in the Pulmonary Department, serologic characteristic of C. pneumoniae infection was found in 34 patients (61,8%). Thirteen of these subjects agreed to participate in the study. They were divided into two groups; placebo was administered to the first one and azithromycin in a dose of 1000 mg once a week--to the other one. The research was conducted using the double blind trial method. Anti-chlamydial antibody level was evaluated before and after treatment. Spirometry tests as well as subjective estimation of physical fitness and dyspnoea degree were also determined. In comparison with 'the placebo group', statistically significant improvement in respiratory parameters 'in the treated group' was not ascertained.

Topics: Adult; Aged; Anti-Bacterial Agents; Asthma; Azithromycin; Chlamydophila Infections; Chlamydophila pneumoniae; Double-Blind Method; Drug Administration Schedule; Female; Humans; Immunoglobulin A; Immunoglobulin G; Male; Middle Aged; Pneumonia, Bacterial; Spirometry; Treatment Outcome

The effect of azithromycin on bronchial hyperresponsiveness was measured in a group of 11 patients with mild asthma. Azithromycin 250 mg orally was administered intermittently to all the patients twice a week for eight weeks. The only other treatment was inhaled beta2 agonist, when required. A histamine inhalation test was performed at the beginning and at the fourth and the eighth week of the study. The mean PC20 values increased significantly over the initial value at the eighth week after the administration of azithromycin (p < 0.05) but mean values for FEV1 and FEV1 percent predicted did not differ significantly. These results suggested that eight weeks of intermittent, low-dose administration of azithromycin in patients with mild asthma might reduce the severity of bronchial hyperresponsiveness.

Topics: Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Severity of Illness Index

Some diseases previously believed to be noninfectious, eg, peptic ulcer disease, are now known to be caused by chronic infection. Recently, chronic Chlamydia pneumoniae infection has been suggested as a cause for adult-onset asthma. The purpose of this study was to determine whether antichlamydial treatment would affect the natural history of this disease.. An open-label, before-after treatment trial was performed in a community-based, primary care office. Forty-six patients (mean age 47.7 years; range 17 to 78) with moderate to moderately severe, stable, chronic asthma were treated a median of 4 weeks (range 3 to 9) with oral doxycycline (100 mg twice daily), azithromycin (1000 mg once weekly), or erythromycin (1000 mg daily). Post-treatment pulmonary function and asthma symptoms were compared with baseline values. Follow-up was an average of 6 months (range 1.5 to 36) post-treatment.. Four patients with C pneumoniae respiratory tract infection developed chronic asthma, which disappeared after treatment in each case. Of the remaining 42 seroreactive patients who were treated a mean of 6 years after the development of chronic asthma, one half had either complete remission or major clinical improvement (3 and 18 patients, respectively). This improvement was significantly more likely to occur in patients with early disease (P = .01) and before the development of fixed obstruction (P < .01).. Antimicrobial therapy appeared to "cure" or significantly improve asthma in approximately one half of treated adults, and the response pattern was consistent with chlamydial pathogenesis. C pneumoniae infection in asthma may be clinically important and should be investigated further.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Asthma; Azithromycin; Child; Chlamydia Infections; Chlamydophila pneumoniae; Chronic Disease; Doxycycline; Erythromycin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Respiratory Function Tests; Time Factors; Treatment Outcome

Asthma is the most frequent chronic airway illness in preschool children and is difficult to diagnose due to the disease's heterogeneity. This study aimed to investigate different machine learning models and suggested the most effective one to classify two forms of asthma in preschool children (predominantly allergic asthma and non-allergic asthma) using a minimum number of features.. After pre-processing, 127 patients (70 with non-allergic asthma and 57 with predominantly allergic asthma) were chosen for final analysis from the Frankfurt dataset, which had asthma-related information on 205 patients. The Random Forest algorithm and Chi-square were used to select the key features from a total of 63 features. Six machine learning models: random forest, extreme gradient boosting, support vector machines, adaptive boosting, extra tree classifier, and logistic regression were then trained and tested using 10-fold stratified cross-validation.. Among all features, age, weight, C-reactive protein, eosinophilic granulocytes, oxygen saturation, pre-medication inhaled corticosteroid + long-acting beta2-agonist (PM-ICS + LABA), PM-other (other pre-medication), H-Pulmicort/celestamine (Pulmicort/celestamine during hospitalization), and H-azithromycin (azithromycin during hospitalization) were found to be highly important. The support vector machine approach with a linear kernel was able to diffrentiate between predominantly allergic asthma and non-allergic asthma with higher accuracy (77.8%), precision (0.81), with a true positive rate of 0.73 and a true negative rate of 0.81, a F1 score of 0.81, and a ROC-AUC score of 0.79. Logistic regression was found to be the second-best classifier with an overall accuracy of 76.2%.. Predominantly allergic and non-allergic asthma can be classified using machine learning approaches based on nine features.. Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Topics: Asthma; Azithromycin; Budesonide; Child, Preschool; Chronic Disease; Hospitalization; Humans; Machine Learning

Obesity is associated with severe asthma, but no specific treatment has been established. The gut microbiome is increasingly recognized as a crucial factor, but specific treatments focused on the gut microbiome have not been established. Recently, azithromycin has been found to have the capacity to attenuate exacerbations, a characteristic of severe asthma. The effect of azithromycin on obesity-induced severe asthma is not understood.. The purpose of the present study is to clarify the effect of azithromycin on exacerbations in asthmatic patients with obesity. To explore the mechanism, the gut microbiome, metabolites of microbes such as short-chain fatty acids, and blood inflammatory cytokines will be analyzed to evaluate the correlation with the effect of azithromycin on exacerbations in obesity-induced severe asthma. A multi-center, prospective, single-arm intervention study is planned.. The present study will allow us to evaluate the effect of azithromycin on exacerbations, particularly in asthma patients with obesity, and explore biomarkers, targeting molecules including the gut microbiome, which are correlated with decreased exacerbations. The present results could contribute to identifying new therapeutic prospects and targeted microbes or molecules associated with severe clinical characteristics in asthmatic patients with obesity.. This study has been registered as a prospective study with the University Hospital Medical Information Network (UMIN0000484389) and the Japan Registry of Clinical Trials (jRCTs071220023).

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Double-Blind Method; Humans; Multicenter Studies as Topic; Obesity; Prospective Studies

Macrolide compounds, many of which are derived from natural sources, all share a lactone ring structure, but of varying sizes. Their biological activities differ with structure and size but tend to overlap. Marketed macrolide drugs include immunosuppressives and antibiotics. Some of the latter have been shown to exert anti-inflammatory activities, due to direct effects on inflammatory cells and processes when used for respiratory infections. Consequently, azithromycin is included in clinical guidelines for COPD and asthma treatment, though it has the disadvantage, as an antibiotic, of increasing bacterial resistance. COPD and asthma, however, like several chronic inflammatory diseases involving other organs, are driven to a large extent by epithelial barrier dysfunction. Recently, azithromycin was shown to directly enhance epithelial barrier function and a new class of derivatives, barriolides, is under development with the lead indication COPD. It is thus likely that by circumventing antibiosis and acting on a crucial etiological disease process, this type of agent will open up a new, safer approach to COPD and asthma therapy with macrolides.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans; Macrolides; Pulmonary Disease, Chronic Obstructive

An important proportion of asthma patients remain uncontrolled despite the use of inhaled corticosteroids and long-acting beta-agonists. Some add-on therapies, like azithromycin, have been recommended for this subgroup of patients. The purpose of this study was to assess the cost-effectiveness of azithromycin as an add-on therapy to ICS + LABA for patients with severe asthma.. A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. The total costs and QALYS of two interventions, including standard therapy (ICS + LABA), and add-on therapy with azithromycin, were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.. The model suggests a potential gain of 0.037 QALYs per patient per year on azithromycin, with a difference of US $718 in favor of azithromycin, showing dominance with respect to SOC. A position of dominance negates the need to calculate an incremental cost-effectiveness ratio. In the deterministic sensitivity analyses, our base-case results were robust to variations in all assumptions and parameters.. Add-on therapy with azithromycin was found to be cost-effective when added to usual care in patients who remain uncontrolled despite treatment with medium or high-dose ICS/LABA.

Topics: Adrenal Cortex Hormones; Asthma; Azithromycin; Humans; Markov Chains; Quality-Adjusted Life Years

To The Editor, The Global Initiative for Asthma (GINA) 2021 update was published on the 28th of April, 2021. There are significant changes, including treatment of mild asthma, the role of azithromycin, treatment of asthma in COVID-19 times, and role of biologics...

Topics: Asthma; Azithromycin; Biological Products; COVID-19; Humans

Excessive production, secretion, and retention of abnormal mucus is a pathological feature of many obstructive airways diseases including asthma. Azithromycin is an antibiotic that also possesses immunomodulatory and mucoregulatory activities, which may contribute to the clinical effectiveness of azithromycin in asthma. The current study investigated these nonantibiotic activities of azithromycin in mice exposed daily to intranasal house dust mite (HDM) extract for 10 days. HDM-exposed mice exhibited airways hyperresponsiveness to aerosolized methacholine, a pronounced mixed eosinophilic and neutrophilic inflammatory response, increased airway smooth muscle (ASM) thickness, and elevated levels of epithelial mucin staining. Azithromycin (50 mg/kg sc, 2 h before each HDM exposure) attenuated HDM-induced airways hyperresponsiveness to methacholine, airways inflammation (bronchoalveolar lavage eosinophil and neutrophils numbers, and IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, and RANTES levels), and epithelial mucin staining (mucous metaplasia) by at least 50% (compared with HDM-exposed mice,

Topics: Adenosine Triphosphate; Allergens; Animals; Asthma; Azithromycin; Disease Models, Animal; Inflammation; Interleukin-13; Metaplasia; Methacholine Chloride; Mice; Mucins; Mucus; Pyroglyphidae

Asthma is a respiratory disease; involving millions of people worldwide. The main cause of asthma is allergy and immune response dysregulation. The effects of azithromycin and doxycycline as asthma-controlling drugs were evaluated in this study. Mice asthma model was produced and asthmatic mice were treated with azithromycin (75 mg/kg, orally) and doxycycline (20 mg/kg, orally). Eosinophils and neutrophils count, interleukin (IL)-4, IL-5, IL-12, IL-13, and total immunoglobulin E (IgE) levels were measured. Histological study and evaluating the genes expression of Muc5ac, Muc5b, IL-33, COX2, MYD88, and TRAF6 were performed. Azithromycin and doxycycline did not affect eosinophil and neutrophil percentage, IL-4, IL-5, IL-12, and total IgE levels, peribronchial and perivascular inflammation, goblet cell hyperplasia, and gene expression of MYD88, TRAF6, and COX2. Treatment with azithromycin significantly decreased IL-13 level, mucus secretion, and gene expression of IL-33, Muc5ac, and Muc5b; compared to the non-treated asthma group. Azithromycin administration controls mucus secretion and inflammation. Azithromycin therapy and not doxycycline might be an effective adjuvant option in asthma with reducing mucus in the airway.

Topics: Animals; Asthma; Azithromycin; Cyclooxygenase 2; Doxycycline; Humans; Immunoglobulin E; Inflammation; Interleukin-12; Interleukin-13; Interleukin-33; Interleukin-5; Mice; Mucus; Myeloid Differentiation Factor 88; Signal Transduction; TNF Receptor-Associated Factor 6

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Child; Humans

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Child; Humans

Low-dose long-term azithromycin is recommended in clinical practice guidelines for obstructive airway diseases (OAD); however, an optimal therapeutic regimen is not yet established.. To understand the patterns of azithromycin use in OAD, characterise the patients who received it and evaluate its safety and efficacy using real-world data.. We audited 91 patients who had received azithromycin for at least 4 weeks for the management of asthma, chronic obstructive pulmonary disease (COPD) or non-cystic fibrosis bronchiectasis.. The mean age was 65 ± 18 years, 60% were female and 48% were ex-smokers. The majority had asthma (75%), either alone (50%) or in combination with COPD (12%) or bronchiectasis (13%). Most (64%) reported cough or sputum at baseline. The most common treatment regimen was azithromycin 250 mg daily (73%) for more than 1 year (57%), with only seven adverse events. There was a significant reduction in the proportions of patients requiring emergency department visits (48% vs 32%; P < 0.001) and hospital admissions (35% vs 31%; P < 0.001) after starting azithromycin. In 88% of cases, physicians favoured the use of azithromycin.. Physicians are currently using low-dose azithromycin for a long duration of more than 1 year for the management of OAD. The typical case definition is an older non-smoking adult with persistent asthma, often in combination with another OAD and presenting with bothersome cough or sputum. Azithromycin was well tolerated and led to reduced healthcare utilisation. Further research is required to establish an optimal dosage regimen of azithromycin in OAD.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiectasis; Cough; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

Add-on azithromycin (AZM) results in a significant reduction in exacerbations among adults with persistent uncontrolled asthma. The aim of this study was to assess the cost-effectiveness of add-on AZM in terms of healthcare and societal costs.The AMAZES trial randomly assigned 420 participants to AZM or placebo. Healthcare use and asthma exacerbations were measured during the treatment period. Healthcare use included all prescribed medicine and healthcare contacts. Costs of antimicrobial resistance (AMR) were estimated based on overall consumption and published estimates of costs. The value of an avoided exacerbation was based on published references. Differences in cost between the two groups were related to differences in exacerbations in a series of net monetary benefit estimates. Societal costs included lost productivity, over the counter medicines, steroid induced morbidity and AMR costs.Add-on AZM resulted in a reduction in healthcare costs (mean (95% CI)) including nights in hospital (AUD 433.70 (AUD 48.59-818.81) or EUR 260.22 (EUR 29.15-491.29)), unplanned healthcare visits (AUD 20.25 (AUD 5.23-35.27) or EUR 12.15 (EUR 3.14-21.16)), antibiotic costs (AUD 14.88 (AUD 7.55-22.21) or EUR 8.93 (EUR 4.53-13.33)) and oral corticosteroid costs (AUD 4.73 (AUD 0.82-8.64) or EUR 2.84 (EUR 0.49-5.18)); all p<0.05. Overall healthcare and societal costs were lower (AUD 77.30 (EUR 46.38) and AUD 256.22 (EUR 153.73) respectively) albeit not statistically significant. The net monetary benefit of add-on AZM was estimated to be AUD 2072.30 (95% CI AUD 1348.55-2805.23) or (EUR 1243.38 (EUR 809.13-1683.14) assuming a willingness to pay per exacerbation avoided of AUD 2651 (EUR 1590.60). Irrespective of the sensitivity analysis applied, the net monetary benefit for total, moderate and severe exacerbations remained positive and significant.Add-on AZM therapy in poorly controlled asthma was a cost-effective therapy. Costs associated with AMR did not influence estimated cost-effectiveness.

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Cost-Benefit Analysis; Humans

Although antibody deficiency (AD) is a well-known cause of recurrent respiratory infections, there are few data on its impact in adults with asthma. The objective of the present study was to assess outcomes in adults with severe asthma and AD after treatment with either azithromycin or subcutaneous immunoglobulins (SCIg).. We performed a 5-year, prospective, observational, two-centre study of adults with severe asthma and AD in France. Bronchiectasis was ruled out by high-resolution computed tomography. Patients were treated for one year with either azithromycin (250 mg every other day) or SCIg (0.4-0.6 g/kg/months, weekly). All patients were evaluated for exacerbations, asthma control and lung function at baseline and then one year after treatment initiation.. Thirty-nine patients with severe asthma were included in the study: 14 had been treated with azithromycin and 25 had been treated with SCIg. Before the initiation of treatment for AD, all patients had an Asthma Control Questionnaire (ACQ-7) score > 1.5 (mean ± SD: 2.71 ± 0.53) despite treatment at GINA step 4 or 5, and had a high exacerbation rate requiring oral corticosteroids and/or rescue antibiotics (∼7.2 ± 2.1/patient/year). One year after treatment initiation, we observed a significantly higher FEV1 (mean: 0.18 ± 0.22 L) and ACQ-7 score (1.26 ± 0.68), and a significantly lower exacerbation rate (1.63 ± 1.24/patient/year).. Treatment of AD dramatically improved asthma outcomes - suggesting that adults with severe asthma and recurrent respiratory infections should be screened and (if appropriate) treated for AD.

Topics: Aged; Asthma; Azithromycin; Disease Progression; Female; Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Injections, Subcutaneous; Male; Middle Aged; Prospective Studies; Respiratory Function Tests; Treatment Outcome

Clinical management of asthma remains a public challenge. Despite standard treatment with inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), asthma remains uncontrolled in a substantial number of chronic asthma patients who risk reduced lung function and severe exacerbations. Azithromycin could have add-on effects for these patients. This study is proposed to systematically evaluate the efficacy of azithromycin as an add-on treatment for adults with persistent uncontrolled symptomatic asthma.. Two reviewers will perform a comprehensive search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and four Chinese electronic databases including China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), WanFang Data and VIP Database from inception to May 2019. Only randomised controlled trials will be included. There is no restriction on language or publication status. Combined oral azithromycin and an ICS or/and a LABA will be compared with standard treatment alone or with a placebo. The primary outcomes are the number or frequency of asthma exacerbations, changes in asthma symptoms and lung function. Secondary outcomes include the number or frequency of inhalations of beta-agonists with or without corticosteroids for rescue use, eosinophil counts in blood or sputum, adverse events and others. A meta-analysis will be attempted to provide an estimate of the pooled treatment effect. Otherwise, qualitative descriptions of individual studies will be given.. Ethical approval is not required because no primary data will be collected. Study findings will be presented at scientific conferences or published in a peer-reviewed journal.. CRD42019117272.

Topics: Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Dose-Response Relationship, Drug; Humans; Meta-Analysis as Topic; Systematic Reviews as Topic; Treatment Outcome

Topics: Allergens; Animals; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchoalveolar Lavage Fluid; Cefixime; Cytokines; Fecal Microbiota Transplantation; Feces; Female; Gastrointestinal Microbiome; Mice, Inbred BALB C; Ovalbumin; Th2 Cells

It's an exciting era of asthma management, with the introduction of several novel modalities, including biological therapy and bronchial thermoplasty.

Topics: Adult; Aged; Aged, 80 and over; Asthma; Azithromycin; Bronchial Thermoplasty; Corticosterone; Female; Humans; Male; Middle Aged; Muscarinic Agonists; Practice Guidelines as Topic; United States

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Immunity, Innate; Pandemics; Pneumonia, Viral; Risk Factors; SARS-CoV-2; Steroids; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Clarithromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests

Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions. We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13-April 11, 2020. The death rate for all hospitalized COVID-19 patients was 8.3%, and median length of hospitalization was 7.5 days. Of the 21 (29% of total) intensive care unit patients, 3 (14.3% died); median length of intensive care unit stay was 12 days. Of the 72 patients, 43 (59.7%) had underlying cardiovascular disease and 19 (26.4%) had underlying pulmonary disease. In this study, death rates were lower than those reported from regions of the United States experiencing a high volume of COVID-19 patients.

Topics: Adenosine Monophosphate; Aged; Aged, 80 and over; Alanine; Asthma; Azithromycin; Betacoronavirus; California; Clinical Laboratory Techniques; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Testing; Diabetes Mellitus; Female; Humans; Hyperlipidemias; Hypertension; Intensive Care Units; Length of Stay; Male; Pandemics; Pneumonia, Viral; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Severity of Illness Index; Survival Analysis; Tomography, X-Ray Computed

Chlamydia pneumoniae is an obligate intracellular bacterium that causes respiratory infection. There may exist an association between C. pneumoniae, asthma, and production of immunoglobulin (Ig) E responses in vitro. Interleukin (IL-4) is required for IgE production.. We previously demonstrated that doxycycline suppresses C. pneumoniae-induced production of IgE and IL-4 responses in peripheral blood mononuclear cells (PBMC) from asthmatic subjects. Whereas macrolides have anti-chlamydial activity, their effect on in vitro anti-inflammatory (IgE) and IL-4 responses to C. pneumoniae have not been studied.. PBMC from IgE- adult atopic subjects (N = 5) were infected +/- C. pneumoniae BAL69, +/- azithromycin (0.1, 1.0 ug/mL) for 10 days. IL-4 and IgE levels were determined in supernatants by ELISA. IL-4 and IgE were detected in supernatants of PBMC (day 10).. When azithromycin (0.1, 1.0 ug/ml) was added, IL-4 levels decreased. At low dose, IgE levels increased and at high dose, IgE levels decreased. When PBMC were infected with C. pneumoniae, both IL-4 and IgE levels decreased. Addition of azithromycin (0.1, 1.0 ug/mL) decreased IL-4 levels and had no effect on IgE levels.. These findings indicate that azithromycin decreases IL-4 responses but has a bimodal effect on IgE responses in PBMC from atopic patients in vitro.

Topics: Aged; Anti-Bacterial Agents; Asthma; Azithromycin; Chlamydophila Infections; Chlamydophila pneumoniae; Female; Humans; Hypersensitivity, Immediate; Immunoglobulin E; In Vitro Techniques; Interleukin-4; Leukocytes, Mononuclear; Male; Middle Aged; Respiratory Tract Infections; Young Adult

Airway smooth muscle (ASM) plays a major role in acute airway narrowing and reducing ASM thickness is expected to attenuate airway hyper-responsiveness and disease burden. There are two therapeutic approaches to reduce ASM thickness: (a) a direct approach, targeting specific airways, best exemplified by bronchial thermoplasty (BT), which delivers radiofrequency energy to the airway via bronchoscope; and (b) a pharmacological approach, targeting airways more broadly. An example of the less well-established pharmacological approach is the calcium-channel blocker gallopamil which in a clinical trial effectively reduced ASM thickness; other agents may act similarly. In view of established anti-proliferative properties of the macrolide antibiotic azithromycin, we examined its effects in naive mice and report a reduction in ASM thickness of 29% (p < .01). We further considered the potential functional implications of this finding, if it were to extend to humans, by way of a mathematical model of lung function in asthmatic patients which has previously been used to understand the mechanistic action of BT. Predictions show that pharmacological reduction of ASM in all airways of this magnitude would reduce ventilation heterogeneity in asthma, and produce a therapeutic benefit similar to BT. Moreover there are differences in the expected response depending on disease severity, with the pharmacological approach exceeding the benefits provided by BT in more severe disease. Findings provide further proof of concept that pharmacological targeting of ASM thickness will be beneficial and may be facilitated by azithromycin, revealing a new mode of action of an existing agent in respiratory medicine.

Topics: Airway Remodeling; Animals; Asthma; Azithromycin; Lung; Male; Mice, Inbred BALB C; Models, Biological; Models, Theoretical; Muscle, Smooth

Topics: Acetates; Adrenergic beta-2 Receptor Antagonists; Amoxicillin-Potassium Clavulanate Combination; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Azithromycin; Betacoronavirus; Budesonide; Convalescence; Coronavirus Infections; COVID-19; Cyclopropanes; Eosinophils; Female; Humans; Hydroxychloroquine; Ipratropium; Male; Middle Aged; Pandemics; Pneumonia, Viral; Quinolines; SARS-CoV-2; Sulfides; Treatment Outcome

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans

Macrolides are antibiotics with anti-inflammatory properties that may be beneficial in the treatment of asthma. In a systematic review, Hiles et al. analysed the effect of azithromycin in the prevention of asthma exacerbations in patients with severe asthma. In their study they conclude that prolonged treatment with azithromycin (at least 3 months) reduces the number of asthma exacerbations; however, the conclusions of this review should be interpreted carefully as the included studies vary in study design, dosing schedule and severity of the asthma. Additionally, maintenance treatment with macrolides may have safety risks, side-effects and lead to antibiotic resistance. Prolonged macrolide therapy should, therefore, be reserved for patients with non-eosinophilic asthma who have no alternative treatment options.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Disease Progression; Drug Resistance, Bacterial; Eosinophils; Humans; Macrolides; Systematic Reviews as Topic

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Child; Child, Preschool; Female; Hospitalization; Humans; Infant; Male; Retrospective Studies

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans; Macrolides

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Drug Resistance, Microbial; Haemophilus influenzae; Humans

Topics: Animals; Asthma; Azithromycin; Bronchodilator Agents; Horse Diseases; Horses; Respiration Disorders

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Disease Progression; Humans

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Disease Progression; Humans

Topics: Adult; Asthma; Azithromycin; Double-Blind Method; Humans; Neutrophils; Quality of Life; Sputum

Azithromycin is a potent agent that prevents airway remodeling. In this study, we hypothesized that azithromycin (35 mg/kg orally) alleviated airway remodeling through suppression of epithelial-to-mesenchymal transition (EMT) via downregulation of transforming growth factor-beta 1 (TGF-β1)/receptor for activated C-kinase1 (RACK1)/snail in mice. An ovalbumin (OVA)-induced Balb/c mice airway allergic inflammatory model was used. Airway inflammation and remodeling were evaluated with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson staining. E-cadherin and N-cadherin (molecular markers of EMT) were analyzed by immunofluorescence, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and western blotting; α-smooth muscle actin (α-SMA) was evaluated using immunohistochemistry (IHC), qRT-PCR, and western blotting; and expression of TGF-β1/RACK1/Snail in lungs was measured by qRT-PCR and western blotting. Our data showed that azithromycin significantly reduced inflammation score, peribronchial smooth muscle layer thickness, goblet cell metaplasia, and deposition of collage fibers (P < 0.05), and effectively suppressed airway EMT (upregulated E-cadherin level, and downregulated N-cadherin and α-SMA levels) compared with the OVA group (P < 0.05). Moreover, the increasing mRNA and protein expressions of TGF-β1 and RACK1 and mRNA level of Snail in lung tissue were all significantly decreased in azithromycin-treated mice (P < 0.05). Taken together, our results suggest that azithromycin has the greatest effects on reducing airway remodeling by inhibiting TGF-β1/RACK1/Snail signal and improving the EMT in airway epithelium.

Topics: Airway Remodeling; Allergens; Animals; Anti-Bacterial Agents; Asthma; Azithromycin; Disease Models, Animal; Epithelial-Mesenchymal Transition; Humans; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Receptors for Activated C Kinase; Respiratory Mucosa; Snail Family Transcription Factors; Transforming Growth Factor beta1

Topics: Adolescent; Anti-Bacterial Agents; Asthma; Azithromycin; Child; Chlamydophila Infections; Chlamydophila pneumoniae; Ciprofloxacin; Doxycycline; Female; Humans; Immunoglobulin E; Interferon-gamma; Interleukin-4; Leukocytes, Mononuclear; Male; Mycoplasma pneumoniae; Young Adult

Early-life use of antibiotics is associated with asthma. We examined the effect of antibiotic use for early-life bronchiolitis on the development of new-onset asthma in children from Taiwan between 2005 and 2010. Data were from the National Health Insurance Research Database 2010, and diseases were coded using the International Classification of Disease (ICD). We classified the patients, all of whom had bronchiolitis, as having asthma or not having asthma. Asthma was diagnosed using ICD criteria and by use of an inhaled bronchodilator and/or corticosteroid twice in one year. We identified age at asthma onset, sex, residential area, history of atopy and NSAID use, age at first use of antibiotics, and the specific antibiotic, and adjusted for these factors using conditional logistic regression analysis. Among all individuals, there was a relationship between risk of new-onset asthma with use of a high dose of an antibiotic (adjusted odds ratio [aOR] = 3.33, 95% confidence interval [CI] = 2.67-4.15). Among the different antibiotics, macrolides (aOR = 2.87, 95% CI = 1.99-4.16), and azithromycin specifically (aOR = 3.45, 95% CI = 1.62-7.36), had the greatest effect of development of asthma.

Topics: Acute Disease; Age Factors; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiolitis; Child, Preschool; Female; Humans; Macrolides; Male; Odds Ratio; Risk Factors; Taiwan

Recent developments in genomics and proteomics enable the discovery of biomarkers that allow identification of subgroups of patients responding well to a treatment. One currently used clinical trial design incorporating a predictive biomarker is the so-called biomarker strategy design (or marker-based strategy design). Conventionally, the results from this design are analysed by comparing the mean of the biomarker-led arm with the mean of the randomised arm. Several problems regarding the analysis of the data obtained from this design have been identified in the literature. In this paper, we show how these problems can be resolved if the sample sizes in the subgroups fulfil the specified orthogonality condition. We also propose a different analysis strategy that allows definition of test statistics for the biomarker-by-treatment interaction effect as well as for the classical treatment effect and the biomarker effect. We derive equations for the sample size calculation for the case of perfect and imperfect biomarker assays. We also show that the often used 1:1 randomisation does not necessarily lead to the smallest sample size. In addition, we provide point estimators and confidence intervals for the treatment effects in the subgroups. Application of our method is illustrated using a real data example.

Topics: Anti-Asthmatic Agents; Asthma; Azithromycin; Biomarkers; Humans; Models, Statistical; Precision Medicine; Randomized Controlled Trials as Topic; Sample Size; Statistics as Topic; Treatment Outcome

Nosotros sugerimos que la TACAR del tórax debió formar parte de la metodología en esta publicación y que constituye una recomendación para la evaluación del Asma refractario al tratamiento en la práctica clínica.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans; Tomography, X-Ray Computed

Topics: Asthma; Azithromycin; Hospitalization; Humans; Pulmonary Disease, Chronic Obstructive

Deficient production of anti-viral interferons (IFNs) may be involved in causing viral-induced asthma exacerbations. Hence, drugs inducing lung IFN production would be warranted. Azithromycin may reduce asthma exacerbations but its modus operandi is unknown. Here, we investigated if azithromycin induces IFNβ expression in vitro in rhinovirus-infected bronchial epithelial cells from asthmatic donors and in vivo in our allergic inflammation-based mouse model of viral stimulus-induced asthma exacerbations. Azithromycin dose-dependently augmented viral-induced IFNβ expression in asthmatic, but not in healthy bronchial epithelial cells. The effect negatively correlated with viral load. Knockdown of MDA5 and RIG-I by siRNA showed involvement of MDA5 but not RIG-I in azithromycin's IFN-inducing effects in vitro. In vivo azithromycin induced IFNβ protein, restoring a reduced lung IFN response exclusively in allergic exacerbating mice. This was associated with induction of interferon-stimulated genes and MDA5, but not RIG-I. We suggest that clinically relevant concentrations of azithromycin produce MDA5-dependent, anti-viral, IFN-inducing effects in bronchial epithelium distinctly from asthmatic donors. Similarly, azithromycin induced MDA5-associated IFN in virally stimulated lungs in vivo exclusively in allergic mice. Effects of azithromycin and MDA5-active drugs on viral-induced exacerbations deserve further research.

Topics: Adult; Animals; Asthma; Azithromycin; Biomarkers; DEAD Box Protein 58; Disease Models, Animal; Disease Progression; Epithelial Cells; Female; Gene Expression; Gene Knockdown Techniques; Humans; Inflammation Mediators; Interferon-beta; Interferon-Induced Helicase, IFIH1; Male; Mice; Picornaviridae Infections; Respiratory Mucosa; Rhinovirus; Virus Replication; Young Adult

This study of the oropharyngeal microbiome complements the previously published AZIthromycin in Severe ASThma (AZISAST) clinical trial, where the use of azithromycin was assessed in subjects with exacerbation-prone severe asthma. Here, we determined the composition of the oropharyngeal microbial community by means of deep sequencing of the amplified 16S rRNA gene in oropharyngeal swabs from patients with exacerbation-prone severe asthma, at baseline and during and after 6 months treatment with azithromycin or placebo.. A total of 1429 OTUs were observed, of which only 59 were represented by more than 0.02% of the reads. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria and Actinobacteria were the most abundant phyla and Streptococcus and Prevotella were the most abundant genera in all the samples. Thirteen species only accounted for two thirds of the reads and two species only, i.e. Prevotella melaninogenica and Streptococcus mitis/pneumoniae, accounted for one fourth of the reads. We found that the overall composition of the oropharyngeal microbiome in patients with severe asthma is comparable to that of the healthy population, confirming the results of previous studies. Long term treatment (6 months) with azithromycin increased the species Streptococcus salivarius approximately 5-fold and decreased the species Leptotrichia wadei approximately 5-fold. This was confirmed by Boruta feature selection, which also indicated a significant decrease of L. buccalis/L. hofstadtii and of Fusobacterium nucleatum. Four of the 8 treated patients regained their initial microbial composition within one month after cessation of treatment.. Despite large diversity of the oropharyngeal microbiome, only a few species predominate. We confirm the absence of significant differences between the oropharyngeal microbiomes of people with and without severe asthma. Possibly, long term azithromycin treatment may have long term effects on the composition of the oropharygeal microbiome in half of the patients.

Topics: Adult; Asthma; Azithromycin; Bacteria; Biodiversity; DNA, Bacterial; Female; Genes, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Male; Microbiota; Middle Aged; Oropharynx; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis; Young Adult

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans; Severity of Illness Index

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Child; Humans

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Azithromycin; Drug Therapy, Combination; Humans; Quality of Life

Azithromycin can benefit treating allergic airway inflammation and remodeling. In the present study, we hypothesized that azithromycin alleviated airway epithelium injury through inhibiting airway epithelium apoptosis via down regulation of caspase-3 and Bax/Bcl2 ratio in vivo and in vitro.. Ovalbumin induced rat asthma model and TGF-β1-induced BEAS-2B cell apoptosis model were established, respectively. In vivo experiments, airway epithelium was stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to histologically evaluate the airway inflammation and remodeling. Airway epithelium apoptotic index (AI) was further analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), while expression of apoptosis related gene (Bax, Bcl2, Caspase-3) in lungs were measured by qRT-PCR and western blotting, respectively. In vitro experiments, apoptosis were evaluated by Flow cytometry (FCM) and TUNEL. Above apoptosis related gene were also measured by qRT-PCR and western blotting.. Compared with the OVA group, azithromycin significantly reduced the inflammation score, peribronchial smooth muscle layer thickness, epithelial thickening and goblet cell metaplasia (P<0.05), and effectively suppressed AI of airway epithelium (P<0.05). Moreover, the increasing mRNA and protein expressions of Caspase-3 and Bax/Bcl-2 ratio in lung tissue were all significantly decreased in azithromycin-treated rats (P<0.05). In vitro, azithromycin significantly suppressed TGF-β1-induced BEAS-2B cells apoptosis (P<0.05) and reversed TGF-β1 elevated Caspase-3 mRNA level and Bax/Bcl-2 ratio (P<0.05).. Azithromycin is an attractive treatment option for reducing airway epithelial cell apoptosis by improving the imbalance of Bax/Bcl-2 ratio and inhibiting Caspase-3 level in airway epithelium.

Topics: Airway Remodeling; Animals; Apoptosis; Asthma; Azithromycin; bcl-2-Associated X Protein; Caspase 3; Cell Line; Endothelium, Vascular; Epithelium; Flow Cytometry; In Situ Nick-End Labeling; Inflammation; Lung; Male; Ovalbumin; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1

We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling.. Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated.. Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group.. This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.

Topics: Animals; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Female; Interleukins; Leukocyte Elastase; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Ovalbumin; Pneumonia; T-Lymphocytes, Helper-Inducer

The aim of this supplement is to provide an introduction to recent advances in the understanding of the impact of microorganisms on the normal and diseased lung for patients with asthma and COPD.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Bronchoalveolar Lavage; Disease Progression; Evidence-Based Medicine; Glucocorticoids; Haemophilus; Humans; Hyperbaric Oxygenation; Male; Microbiota; Middle Aged; Moraxella; Muscarinic Antagonists; Nebulizers and Vaporizers; Neisseriaceae; Practice Guidelines as Topic; Primary Health Care; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Child, Preschool; Humans; Male; Postoperative Complications; Radiography, Thoracic; Subcutaneous Emphysema; Treatment Outcome

To discuss the clinical effects of treating secondary asthma attacks of children Mycoplasma pneumoniae with combined therapy of montelukast and azithromycin.. 96 children patients diagnosed with secondary asthma attacks of Mycoplasma pneumonia were enrolled in this study. They were randomly divided into two groups: the control group (n=49) and the observation group (n=47). Patients in the control group received combined therapy using azithromycin and bronchodilators or glucocorticoid, and patients in the observation group received a combined therapy of montelukast, azithromycin and bronchodilators or glucocorticoid. The lung function indexes, T lymphocyte subpopulation, cytokines levels, positive rate of lgG and lgM, asthma control rate and recurrence rate were compared between groups before and after treatment.. The levels of V-T, t-PTEF/t-E, MTIF/MTEF and TEF25/PTEF in both groups increased after treatment, but we observed a more significant improvement in the observation group. The CD4+ and CD4+/CD8+ levels in both groups also increased after the intervention, while the level of CD8+ decreased. The IL-10, IL-17 and TGF-β levels decreased more intensely in the observation group.. The positive rate of lgG and lgM in both groups decreased significantly after the intervention. In the observation group, the asthma control rate was higher while the recurrence rate was lower. Although montelukast had little effect on improving the immune function, it was certainly beneficial for controlling the symptoms of asthma and improving the prognosis.. Using combined therapy of montelukast and azithromycin for treating the secondary asthma attacks of children mycoplasma pneumonia can relieve immunological and inflammatory reactions and improve the lung function.

Topics: Acetates; Asthma; Azithromycin; Child; Cyclopropanes; Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Quinolines; Sulfides

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiolitis Obliterans; Chlamydophila Infections; Clarithromycin; Female; Haemophilus Infections; Humans; Lung Transplantation; Male

Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associated with Haemophilus influenzae colonization. Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy. Using a mouse model of infection, we show that corticosteroid treatment promotes H. influenzae persistence. Transcriptomic analysis of bacteria either isolated from infected mouse airway or grown in laboratory medium identified a number of genes encoding regulatory factors whose expression responded to the presence of glucocorticosteroids. Importantly, a number of these corticosteroid-responsive genes also showed elevated expression in H. influenzae within sputum from asthma patients undergoing steroid treatment. Addition of corticosteroid to H. influenzae led to alteration in biofilm formation and enhanced resistance to azithromycin, and promoted azithromycin resistance in an animal model of respiratory infection. Taken together, these data strongly suggest that H. influenzae can respond directly to corticosteroid treatment in the airway potentially influencing biofilm formation, persistence and the efficacy of antibiotic treatment.

Topics: Animals; Anti-Bacterial Agents; Asthma; Azithromycin; Biofilms; Disease Models, Animal; Drug Resistance, Bacterial; Gene Expression Profiling; Glucocorticoids; Haemophilus Infections; Haemophilus influenzae; Humans; Mice; Sputum

Topics: Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Bacteria; Bronchoscopy; Humans

A new concept in design of safe glucocorticoid therapy was introduced by conjugating potent glucocorticoid steroids with macrolides (macrolactonolides). These compounds were synthesized from various steroid 17β-carboxylic acids and 9a-N-(3-aminoalkyl) derivatives of 9-deokso-9a-aza-9a-homoeritromicin A and 3-descladinosyl-9-deokso-9a-aza-9a-homoeritromicin A using stable alkyl chain. Combining property of macrolides to preferentially accumulate in immune cells, especially in phagocyte cells, with anti-inflammatory activity of classic steroids, we designed molecules which showed good anti-inflammatory activity in ovalbumin (OVA) induced asthma in rats. The synthesis, in vitro and in vivo anti-inflammatory activity of this novel class of compounds are described.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Carboxylic Acids; Cell Line; Drug Design; Glucocorticoids; Macrolides; Male; Mice; Mice, Inbred BALB C; Rats; Rats, Inbred BN; Steroids

Chronic C. pneumoniae infection has been suggested as a cause for adult onset of asthma. There are data to suggest that infectious organisms, particularly the atypical bacteria C. pneumoniae, may be involved in asthma pathogenesis. The significance of these organisms is as yet unclear. It is not known whether this organism was allowed to persist after an infection, or was present prior to the development of asthma. The purpose of this study was to determine whether anti-chlamydial treatment with azithromycin will improve asthma symptoms and lung function in asthmatic patients positive for C. pneumoniae. For this purpose, 20 patients (mean age 39.8 years) with mild asthma were treated a median of 8 weeks with azithromycin 1000 mg once weekly. All patients had C. pneumoniae infection detected by Seeplex Multiplex PCR in sputum and positive IgG titre>1:64 and IgA titre>1:16 antibodies against C. pneumoniae. Post treatment lung function, symptom score (cough, wheezing, dyspnea), morning and evening PEF values and β2-agonist use were compared with baseline values. After 8 weeks of treatment with azithromycin there was a significant reduction in symptom score (p<0.001) and a significant improvement in lung function FEV1 (p<0.001), morning and evening PEF values p<0.05 Wilcoxon matched Pairs test. We also found a reduction in β2-agonist use, but it was not statistically significant. Treatment with azithromycin significantly improved asthma symptoms and lung function, indicating that C. pneumoniae may play an important role in enhancing the inflammatory processes in the lower airways.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Chlamydia Infections; Chlamydophila pneumoniae; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Peak Expiratory Flow Rate; Pneumonia, Bacterial; Recovery of Function; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Chronic Disease; Humans

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Female; Humans; Male

Several Chlamydia pneumoniae (Cp) biomarkers have been associated with asthma but Cp-specific IgE (Cp IgE) has not been investigated extensively. Our objective was to investigate Cp IgE in community adult asthma patients.. (1) Prevalence of Cp IgE (measured by immunoblotting) and Cp DNA (by polymerase chain reaction) in peripheral blood, and biomarker associations with asthma severity. (2) Case-control studies of Cp IgE association with asthma using healthy blood donor (study 1) and non-asthmatic clinic patient (study 2) controls.. Of 66 asthma subjects (mean age 40.9 years, range 5-75, 59% male, 45% ever-smokers) 33 (50%) were Cp IgE positive and 16 (24%) were Cp DNA positive (P = 0.001 for association of Cp IgE and DNA). Cp IgE was detected in 21% of mild intermittent asthma v 79% of severe persistent asthma (test for trend over severity categories, P = 0.002). Cp IgE detection was significantly (P = 0.001) associated with asthma when compared to healthy blood donor controls but not when compared to clinic controls.. Half of this sample of community asthma patients had detectable IgE against C. pneumoniae. Cp IgE was strongly and positively associated with asthma severity and with asthma when healthy blood donor controls were used. These results support the inclusion of Cp IgE as a biomarker in future studies of infectious contributions to asthma pathogenesis.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antibodies, Bacterial; Asthma; Azithromycin; Case-Control Studies; Child; Chlamydophila Infections; Chlamydophila pneumoniae; Female; Humans; Immunoglobulin E; Male; Middle Aged; Young Adult

Childhood asthma is a type 2 helper T (Th2) cell-driven inflammatory airway disease characterized by recurrent episodes of airway obstruction. Azithromycin (AZM), a macrolide antibiotic exhibiting anti-inflammatory activity aside from its antibacterial effect, may prove beneficial for asthmatic children. This study aimed to determine the effect of AZM on Th2 cells from atopic asthmatic children and non-atopic controls.. CD4+ cells were isolated from peripheral blood mononuclear cells of 9 patients with asthma and 9 non-atopic individuals. Cells were activated as Th0 and differentiated into Th2 cells. The effect of AZM on activated CD4+ cells was evaluated with respective cell proliferation and cytokine production.. Th0 and Th2 CD4+ T cells from atopic asthmatic children produced greater interleukin (IL)-5 (Th2 cytokine) but lower interferon (IFN)-γ (Th1 cytokine) compared to the non-atopic controls, respectively. AZM inhibited IL-5 production of Th0 and Th2 cells from atopic asthmatics in a dose-dependent fashion, without significantly affecting their IL-13 and IFN-γ production. A similar effect was observed in non-atopic controls except that AZM did inhibit IFN-γ production of their Th0 cells. AZM at a higher dose decreased cell viability by inhibiting CD4+ T cell proliferation and enhanced their apoptosis, an effect similarly observed in Th0 and Th2 cells, and did not differ between asthmatic children and controls.. Our finding that AZM preferentially downregulates IL-5 production suggests its therapeutic potentials in controlling childhood asthma.

Topics: Anti-Inflammatory Agents; Apoptosis; Asthma; Azithromycin; Cell Survival; Child; Flow Cytometry; Humans; Interferon-gamma; Interleukin-13; Interleukin-5; Lymphocyte Activation; Statistics, Nonparametric; Th2 Cells

Previous studies have demonstrated that long-term low-dose macrolides are efficacious in cystic fibrosis (CF) and diffuse panbronchiolitis, two chronic neutrophilic airway diseases.. The aims of this study were to evaluate the efficacy and safety of low-dose neomacrolides as add-on therapy in patients with severe asthma and/or bronchiectasis and to identify predictors for therapeutic response.. In a retrospective observational cohort study, we examined 131 adult, non-CF patients with severe asthma and/or bronchiectasis, receiving low-dose neomacrolides as add-on treatment. Pulmonary function tests and symptom scores were assessed at baseline and after 3 to 8 weeks of therapy.. After 3-8 weeks of treatment with low-dose neomacrolides, 108 patients were available for evaluation. In asthma patients (n = 47), pulmonary function tests and symptom scores improved significantly. Responders (≥7% forced expiratory volume in one second predicted [FEV(1)%] improvement) were older (55 vs. 47 years; p = 0.042) and had a longer duration of asthma (29 vs. 9 years; p = 0.052). In patients with bronchiectasis only (n = 61), symptom scores improved significantly. Responders (≥60% symptom score improvement) were older (61 vs. 53 years; p = 0.004), more frequently male (53% vs. 27%; p = 0.043), and there was a nonsignificant trend towards higher high-resolution CT (HRCT) score for bronchiectasis in responders (6.4 vs. 4.6; p = 0.053). In multivariate logistic regression analysis, age and male gender were independent predictors for improvement in this group.. The results of this retrospective study suggest that neomacrolides may be useful as an add-on therapy in patients with severe asthma and/or bronchiectasis. Older age may predict good response in patients with severe asthma, whereas older age, male gender and a higher HRCT score for bronchiectasis may predict therapeutic response in patients with bronchiectasis only. Prospective controlled trials of neomacrolides in patients with severe asthma are needed to confirm these observations.

Topics: Adult; Age Factors; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiectasis; Clarithromycin; Cohort Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Respiratory Function Tests; Retrospective Studies; Severity of Illness Index; Sex Factors; Treatment Outcome

Pseudoachondroplasia (PsA) is a type of short-limbed dwarfism resulting from mutations in the cartilage oligomeric matrix protein gene. Skeletal involvement in the PsA is well-described but there are not any published cases reporting airways involvement. The authors present a case of a female with the PsA and congenital anomalies of the respiratory tract resulting in the tracheobronchomalacia and a difficult to control asthma.

Topics: Achondroplasia; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Anti-Bacterial Agents; Anti-Inflammatory Agents; Asthma; Azithromycin; Female; Humans; Middle Aged; Prednisolone; Pulmonary Artery; Tracheobronchomalacia

Definitive conclusions regarding the antiinflammatory effects of macrolide antibiotics for treatment of asthma are difficult to formulate since their beneficial effects may be related to their antimicrobial action. We hypothesized that azithromycin possesses distinct antiinflammatory properties and tested this assumption in a noninfectious mouse model of allergic asthma.. To induce allergic airway inflammation, 7-week-old BALB/cJ mice underwent intraperitoneal ovalbumin sensitization on days 0 and 7 followed by an intranasal challenge on day 14. Mice were treated with azithromycin or phosphate-buffered saline (PBS) solution on days 13 through 16. On day 17, airway inflammation was assessed by quantifying leukocytes in the airway, expression of multiple inflammatory mediators in the BAL fluid, and mucous cell metaplasia. In a separate set of experiments, azithromycin or PBS solution treatment were initiated after the ovalbumin challenge. Each experiment was repeated 3 times (a total of 9 to 11 mice in each group).. Compared to treatment with PBS solution, azithromycin attenuated the ovalbumin-dependent airway inflammation. We observed a decrease in total leukocytes in the lung tissue and BAL fluid. In addition, azithromycin attenuated the expression of cytokines (eg, interleukin [IL]-13 and IL-5) and chemokines (eg, CCL2, CCL3, and CCL4) in the BAL fluid and abrogated the extent of mucous cell metaplasia. Similar antiinflammatory effects were observed when azithromycin treatment was initiated after the ovalbumin challenge.. In this noninfectious mouse model of allergic asthma, azithromycin attenuated allergic airway inflammation. These findings demonstrate an antiinflammatory effect of azithromycin and suggest azithromycin may have beneficial effects in treating noninfectious airway inflammatory diseases, including asthma.

Topics: Animals; Asthma; Azithromycin; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Immunoglobulin E; Inflammation; Inflammation Mediators; Leukocyte Count; Lung; Mice; Mice, Inbred BALB C; Mucous Membrane; Ovalbumin; Random Allocation; Reference Values; Risk Factors; Sensitivity and Specificity

To study effects of eradication of Chlamydophila pneumoniae CP) infection in bronchial asthma (BA) on BA course and changes in quality of life (QOL) in BA patients.. 194 BA patients in clinical remission participated in the trial. Microbiological diagnosis of asymptomatic CP infection was made serologically (ELISA, indirect enzyme immunoassay) using polymerase chain reaction. Clinical and biochemical tests, assessment of pulmonary ventilation function, QOL by AQLQ during 6-week antimicrobial therapy were made in 56 patients.. Patients with stable BA had high frequency of serological signs of clinically asymptomatic CP infection (52%) deteriorating BA symptoms and QOL. Antibacterial therapy of latent CP infection with azitromycin significantly improved BA course and QOL of BA patients.. When laboratory tests detect CP infection in patients with long-term course of BA, especially in smoking males with moderate and severe BA it is clinically valid to prescribe addition of azitromycin to basic antiinflammatory treatment of BA.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Chlamydophila Infections; Chlamydophila pneumoniae; Female; Humans; Male; Middle Aged; Quality of Life

Chlamydia pneumoniae is an obligate intracellular respiratory pathogen capable of persistent infection. Seroepidemiologic studies and the results of open-label antimicrobial treatment of patients with non-steroid-dependent asthma have suggested a potential role for C. pneumoniae in asthma.. To evaluate the results of antimicrobial treatment in patients with uncontrolled steroid-dependent asthma and serologic evidence suggesting C. pneumoniae infection.. Three nonsmoking asthmatic patients (aged 13 to 65 years) whose symptoms remained poorly controlled despite daily administration of inhaled and oral steroid (10 to 40 mg/d). All met serologic criteria for current or recent C. pneumoniae infection.. After prolonged treatment (6 to 16 weeks) with clarithromycin or azithromycin all three patients were able to discontinue oral steroids. All three patients have remained well controlled with inhaled antiasthma therapy only during 3 to 24 months of postantibiotic therapy observation.. In adolescent and adult asthmatic patients, Chlamydia pneumoniae infection may contribute to symptoms of asthma that are poorly controlled by steroids. Serologic evidence for C. pneumoniae infection should be sought in such patients. A trial of appropriate antibiotic therapy may be helpful in those patients with high titers of anti-C. pneumoniae IgG antibodies.

Topics: Administration, Inhalation; Adolescent; Aged; Anti-Bacterial Agents; Antibodies, Bacterial; Asthma; Azithromycin; Chlamydia Infections; Chlamydophila pneumoniae; Clarithromycin; Female; Glucocorticoids; Humans; Immunoglobulins; Male; Middle Aged; Nebulizers and Vaporizers

Macrolides are known to have relatively few side effects and are prescribed in cases of allergic reaction to penicillin. The new macrolides, for example Azithromycin and Roxithromycin, are increasingly preferred over erythromycin at the ear, nose, and throat out-patient department due to improved oral reabsorption (acid resistance), better penetration into tissue, prolonged half-life, extended antibacterial activity, modest side effects, and better pharmacokinetics. There are only few case reports concerning side effects of macrolides. We report on the appearance of a Churg Strauss-Syndrome (CSS) in a patient following intake of the macrolide antibiotic azithromycin and roxithromycin.. A 50-year-old patient with asthma for three years presented with arthritis and mononeuritis multiplex. Laboratory and radiological investigations revealed eosinophilia (64%), eosinophilic infiltrations of bone marrow, raised IgE-level, and transient pulmonary infiltrates. THERAPY AND DEVELOPMENT: Intravenous steroid therapy was started and resulted in normalization of eosinophilia, IgE-level, and asthmatic symptoms. The neurologic deficits showed only a weak tendency for improvement.. The diagnosis of CSS was established on the basis of clinical criterias and laboratory investigations. The diagnosis was supported by the fact that a similar course of the disease was observed one year ago following administration of azithromycin, another macrolide.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Churg-Strauss Syndrome; Drug Hypersensitivity; Ethmoid Sinusitis; Humans; Maxillary Sinusitis; Middle Aged; Recurrence; Retreatment; Roxithromycin

The effects of the macrolide antimicrobial agents azithromycin, clarithromycin, erythromycin and roxithromycin on the prooxidative activity of stimulated human neutrophils have been investigated in vitro. Superoxide generation by activated neutrophils was measured by lucigenin-enhanced chemiluminescence. At the concentrations used (2.5-80 micrograms/ml) none of the test agents was cytotoxic, nor did they possess superoxide-scavenging properties. Treatment of neutrophils with all 4 macrolides was accompanied by dose-related inhibition of superoxide production by cells activated with FMLP or the calcium ionophore (A23187), while the responses activated by phorbol myristate acetate (PMA) or opsonized zymosan were minimally affected. The anti-oxidative interactions of roxithromycin with FMLP-activated neutrophils were neutralized by pretreatment of the cells with low, non-cytotoxic concentrations (0.5 microgram/ml) of the prooxidative, proinflammatory bioactive phospholipids, lysophosphatidylcholine (LPC), platelet-activating factor (PAF) and lyso-PAF (LPAF). Using an assay of membrane-stabilizing activity, the macrolides antagonized the membrane-disruptive effects of LPC, PAF and LPAF, without affecting enzymes involved in their synthesis. These membrane-stabilizing interactions of macrolides with neutrophils may counteract the proinflammatory, prooxidative activity of several bioactive lipids which have been implicated in the pathogenesis of bronchial asthma.

Topics: Adult; Anti-Asthmatic Agents; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Azithromycin; Calcimycin; Cell Membrane; Clarithromycin; Erythromycin; Humans; Ionophores; Luminescent Measurements; Lysophosphatidylcholines; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Activating Factor; Respiratory Burst; Roxithromycin; Superoxides; Tetradecanoylphorbol Acetate; Zymosan