zithromax and Bronchiolitis

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

To systematically evaluate the clinical effect of azithromycin (AZM) adjuvant therapy in children with bronchiolitis.. Related databases were searched for randomized controlled trials (RCTs) on AZM adjuvant therapy in children with bronchiolitis published up to February 17, 2019. RevMan 5.3 was used to perform the Meta analysis.. A total of 14 RCTs were included, with 667 children in the intervention group and 651 in the control group. The pooled effect size showed that in the children with bronchiolitis, AZM adjuvant therapy did not shorten the length of hospital stay (MD=-0.29, 95%CI: -0.62 to 0.04, P=0.08) or oxygen supply time (MD=-0.33, 95%CI: -0.73 to 0.07, P=0.10), while it significantly shortened the time to the relief of wheezing (MD=-1.00, 95%CI: -1.72 to -0.28, P=0.007) and cough (MD=-0.48, 95%CI: -0.67 to -0.29, P<0.00001). The analysis of bacterial colonization revealed that AZM therapy significantly reduced the detection rates of Streptococcus pneumoniae (OR=0.24, 95%CI: 0.11-0.54, P=0.0006), Haemophilus (OR=0.28, 95%CI: 0.14-0.55, P=0.0002), and Moraxella catarrhalis (OR=0.21, 95%CI: 0.11-0.40, P<0.00001) in the nasopharyngeal region.. AZM adjuvant therapy can reduce the time to the relief of wheezing and cough in children with bronchiolitis, but it has no marked effect on the length of hospital stay and oxygen supply time.

Topics: Azithromycin; Bronchiolitis; Child; Combined Modality Therapy; Humans; Length of Stay; Respiratory Sounds

Diffuse panbronchiolitis (DPB) is a rare progressive and eventually fatal pulmonary disease first identified in Japan and initially seen predominantly in Southeast Asia. Macrolide antibiotics rapidly reverse symptoms and pathology, and their use increased the 5 and 10-year survival from 50 and 30 percent, respectively, to over 90%. Review of 181 case reports from previous publications found patients with DPB commonly had their pulmonary symptoms preceded by rhinosinusitis, frequently by many years. Long delays in diagnosis for many years were common. The review further identified DPB in all ethnic groups and multiple areas outside of Southeast Asia. Although diagnosis was most commonly made in adults, 13% of the diagnoses were made in children and nine of the adult cases described onset in childhood. Few cases of relapse were reported, but extended periods of monitoring after treatment were not generally present.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Haemophilus Infections; Humans; Prognosis

Macrolides may attenuate airway inflammation of bronchiolitis with anti-inflammatory and antiviral effects. However, the potential mechanisms of action underlying the efficiency of macrolides in treating bronchiolitis are limited. Therefore, we performed a meta-analysis to assess the effects of macrolides on airway microbiome and cytokine of children with bronchiolitis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched until May 2018. The reference lists of included studies and pertinent reviews were investigated for supplementing our search. Randomized controlled trials (RCTs) that compared macrolides with placebo assessing the change of microbiome in airway and cytokine were included. A total of four RCTs were included in this review. Data analysis showed no significant reduction of viruses at 48 hr after azithromycin treatment (p = 0.41). There were significant reductions in Streptococcus pneumoniae (risk ratio [RR] 0.28, 95% confidence interval (CI) 0.14 to 0.6, p < 0.01), Haemophilus influenza (RR 0.35, 95% CI 0.2 to 0.62, p < 0.01), and Moraxella catarrhalis (RR 0.29, 95% CI 0.17 to 0.5, p < 0.01), but no significant reduction of Staphylococcus aureus (p = 0.28) following treatment with macrolides. There was a significant decrease in the serum interleukin-8(IL-8), interleukin-4(IL-4), and eotaxin levels following 3 weeks of clarithromycin therapy. There was no significant difference in the serum IL-8 level at Day 15 after the intervention between the azithromycin and control groups; however, a significant reduction of nasal lavage IL-8 level was found. The macrolides may reduce the IL-8 levels in the airway and plasma, but failed to demonstrate an antiviral effect in children with bronchiolitis.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Cytokines; Databases, Factual; Haemophilus influenzae; Humans; Infant; Interleukin-4; Interleukin-8; Macrolides; Microbiota; Moraxella; Respiratory System; Staphylococcus aureus; Streptococcus pneumoniae

In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Chronic Disease; Clarithromycin; Erythromycin; Haemophilus Infections; History, 20th Century; History, 21st Century; Humans; Japan; Macrolides; Nasal Polyps; Rhinitis; Sinusitis

Bronchiolitis is a serious, potentially life-threatening respiratory illness commonly affecting babies. It is often caused by respiratory syncytial virus (RSV). Antibiotics are not recommended for bronchiolitis unless there is concern about complications such as secondary bacterial pneumonia or respiratory failure. Nevertheless, they are often used.. To evaluate the effectiveness of antibiotics for bronchiolitis in children under two years of age compared to placebo or other interventions.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 6), which includes the Cochrane Acute Respiratory Infection Group's Specialised Register, and the Database of Abstracts of Reviews of Effects, MEDLINE (1966 to June 2014), EMBASE (1990 to June 2014) and Current Contents (2001 to June 2014).. Randomised controlled trials (RCTs) comparing antibiotics to placebo in children under two years diagnosed with bronchiolitis, using clinical criteria (including respiratory distress preceded by coryzal symptoms with or without fever). Primary clinical outcomes included time to resolution of signs or symptoms (pulmonary markers included respiratory distress, wheeze, crepitations, oxygen saturation and fever). Secondary outcomes included hospital admissions, length of hospital stay, readmissions, complications or adverse events and radiological findings.. Two review authors independently analysed the search results.. We included seven studies with a total of 824 participants. The results of these seven included studies were often heterogeneous, which generally precluded meta-analysis, except for deaths, length of supplemental oxygen use and length of hospital admission.In this update, we included two new studies (281 participants), both comparing azithromycin with placebo. They found no significant difference for length of hospital stay, duration of oxygen requirement and readmission. These results were similar to an older study (52 participants) that demonstrated no significant difference comparing ampicillin and placebo for length of illness.One small study (21 participants) with higher risk of bias randomised children with proven RSV infection to clarithromycin or placebo and found a trend towards a reduction in hospital readmission with clarithromycin.The three studies providing adequate data for days of supplementary oxygen showed no difference between antibiotics and placebo (pooled mean difference (MD) (days) -0.20; 95% confidence interval (CI) -0.72 to 0.33). The three studies providing adequate data for length of hospital stay, similarly showed no difference between antibiotics (azithromycin) and placebo (pooled MD (days) -0.58; 95% CI -1.18 to 0.02).Two studies randomised children to intravenous ampicillin, oral erythromycin and control and found no difference for most symptom measures.There were no deaths reported in any of the arms of the seven included studies. No other adverse effects were reported.. This review did not find sufficient evidence to support the use of antibiotics for bronchiolitis, although research may be justified to identify a subgroup of patients who may benefit from antibiotics. Further research may be better focused on determining the reasons that clinicians use antibiotics so readily for bronchiolitis, how to reduce their use and how to reduce clinician anxiety about not using antibiotics.

Topics: Ampicillin; Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Clarithromycin; Erythromycin; Humans; Infant; Length of Stay; Randomized Controlled Trials as Topic

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

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Chronic Disease; Clarithromycin; Erythromycin; History, 20th Century; Humans; Japan; Lung Neoplasms; Respiratory Tract Infections

Ensuring adherence to treatment and retention is important in clinical trials, particularly in remote areas and minority groups. We describe a novel approach to improve adherence, retention and clinical review rates of Indigenous children.. This descriptive study was nested within a placebo-controlled, randomised trial (RCT) on weekly azithromycin (or placebo) for 3-weeks. Indigenous children aged ≤24-months hospitalised with acute bronchiolitis were recruited from two tertiary hospitals in northern Australia (Darwin and Townsville). Using mobile phones embedded within a culturally-sensitive approach and framework, we report our strategies used and results obtained. Our main outcome measure was rates of adherence to medications, retention in the RCT and self-presentation (with child) to clinic for a clinical review on day-21.. Of 301 eligible children, 76 (21%) families declined participation and 39 (13%) did not have access to a mobile phone. 186 Indigenous children were randomised and received dose one under supervision in hospital. Subsequently, 182 (99%) children received dose two (day-7), 169 (93%) dose three (day-14) and 180 (97%) attended their clinical review (day-21). A median of 2 calls (IQR 1-3) were needed to verify adherence. Importantly, over 97% of children remained in the RCT until their clinical endpoint at day-21.. In our setting, the use of mobile phones within an Indigenous-appropriate framework has been an effective strategy to support a clinical trial involving Australian Indigenous children in urban and remote Australia. Further research is required to explore other applications of this approach, including the impact on clinical outcomes.. ACTRN12608000150347 (RCT component).

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Cell Phone; Female; Health Services, Indigenous; Humans; Infant; Male; Medication Adherence; Native Hawaiian or Other Pacific Islander; Northern Territory; Reminder Systems

Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O2) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology.. Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48 hrs later. Primary endpoints (LOS, O2) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected.. 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O2 requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours.. Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O2 requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Double-Blind Method; Female; Humans; Infant; Length of Stay; Male; Placebos

Acute lower respiratory infections are the commonest cause of morbidity and potentially preventable mortality in Indigenous infants. Infancy is also a critical time for post-natal lung growth and development. Severe or repeated lower airway injury in very young children likely increases the likelihood of chronic pulmonary disorders later in life. Globally, bronchiolitis is the most common form of acute lower respiratory infections during infancy. Compared with non-Indigenous Australian infants, Indigenous infants have greater bacterial density in their upper airways and more severe bronchiolitis episodes. Our study tests the hypothesis that the anti-microbial and anti-inflammatory properties of azithromycin, improve the clinical outcomes of Indigenous Australian infants hospitalised with bronchiolitis.. We are conducting a dual centre, randomised, double-blind, placebo-controlled, parallel group trial in northern Australia. Indigenous infants (aged ≤ 24-months, expected number = 200) admitted to one of two regional hospitals (Darwin, Northern Territory and Townsville, Queensland) with a clinical diagnosis of bronchiolitis and fulfilling inclusion criteria are randomised (allocation concealed) to either azithromycin (30 mg/kg/dose) or placebo administered once weekly for three doses. Clinical data are recorded twice daily and nasopharyngeal swab are collected at enrollment and at the time of discharge from hospital. Primary outcomes are 'length of oxygen requirement' and 'duration of stay,' the latter based upon being judged as 'ready for respiratory discharge'. The main secondary outcome is readmission for a respiratory illness within 6-months of leaving hospital. Descriptive virological and bacteriological (including development of antibiotic resistance) data from nasopharyngeal samples will also be reported.. Two published studies, both involving different patient populations and settings, as well as different macrolide antibiotics and treatment duration, have produced conflicting results. Our randomised, placebo-controlled trial of azithromycin in Indigenous infants hospitalised with bronchiolitis is designed to determine whether it can reduce short-term (and potentially long-term) morbidity from respiratory illness in Australian Indigenous infants who are at high risk of developing chronic respiratory illness. If azithromycin is efficacious in reducing the morbidly of Indigenous infants hospitalised with bronchiolitis, the intervention would lead to improved short term (and possibly long term) health benefits.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Child, Preschool; Double-Blind Method; Humans; Infant; Infant, Newborn; Length of Stay; Native Hawaiian or Other Pacific Islander; Northern Territory; Oxygen Inhalation Therapy; Patient Readmission; Placebo Effect; Queensland; Recurrence; Research Design; Time Factors; Treatment Outcome

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Female; Humans; Male; Middle Aged; Respiratory Function Tests; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Biomarkers; Bronchiolitis; C-Reactive Protein; Cystic Fibrosis; Double-Blind Method; Humans; Male; Quality of Life; Treatment Outcome; Vital Capacity

In the treatment of diffuse panbronchiolitis, azithromycin (AZM), a new macrolide antibiotic with 15-membered lactone ring, was studied for its efficacy and safety. AZM, 250 mg, was intermittently administered to a total of 60 patients twice a weeks, for 3 months as a rule, and its efficacy was clinically evaluated in 52 patients and the safety in 55. The rate of efficacy was 84.6% (44/52). Clinical findings 12 weeks after the start of administration showed a decrease in sputum volume in 30 of 46 patients and amelioration of dyspnea on exertion in 23 of 46 patients, and no worsening of symptoms was observed in the patients. Vital capacity (4/22), FEV1.0 (6/21), cold agglutination reaction (22/28), and CRP (16/36) were also improved. The rate of eradication of organisms isolated from the sputum except for indigenous organisms was 39.5% (15/38); 4 of the 22 strains of Pseudomonas aeruginosa were eradicated. Adverse reactions were observed in 4 of the 55 patients (7.3%), 1 patient each with rash, itching, diarrhea, and a gastric symptom (heavy feeling in the stomach). 4 of the 54 patients (7.4%) exhibited abnormal changes in clinical laboratory test values values. These were an increase in eosinophil count in 2, elevation of GOT in 1, and elevation of Al-P in 1. These adverse reactions and abnormal changes in laboratory tests were mild or moderate. Therefore, long-term intermittent administration of AZM, twice a week, is expected to have the same effect in the treatment of diffuse panbronchiolitis as long-term small-dose administration of 14-membered macrolides such as erythromycin and clarithromycin, whose effects have already been established.

Topics: Adolescent; Adult; Aged; Azithromycin; Bacterial Infections; Bronchiolitis; Drug Administration Schedule; Female; Humans; Japan; Male; Middle Aged

Topics: Azithromycin; Bronchiolitis; Bronchiolitis Obliterans; Humans; Respiratory Sounds

Azithromycin (AZM), that is a macrolide antibiotic, has been found to treat diffuse panbronchiolitis (DPB) effectively. However, the mechanism of action underlying the therapeutic effects remains unclear. We selected 64 patients with DPB from 305 patients who were diagnosed with DPB at the outpatient clinic in Shanghai Pulmonary Hospital from Jan 2010 to Oct 2014. The primary PBLs, CD4 + T cells, and Jurkat T cells were treated with AZM or erythromycin (EM), and the effects of AZM and EM on IL-17A and CXCL-2 production, proliferation, apoptosis and autophagy were evaluated. AZM and EM significantly inhibited IL-17A and CXCL-2 production in patients' PBLs (all P < 0.05). AZM significantly inhibited proliferation and promoted apoptosis of T cells from DPB patients. AZM can enhance autophagosome formation of T cells by suppressing S6RP phosphorylation, which is a downstream target of mTOR pathway (all P < 0.05). AZM and EM significantly decreased secreted IL-17A levels (P < 0.05) in the primary CD4 + T cells of patients with DPB. AZM may treat DPB patients by targeting cytokine production, proliferation, apoptosis and autophagy of T cell. The mechanism of therapeutic effects of AZM on DPB may be associated with a specific inhibition of mTOR pathway in the T lymphocytes.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Dose-Response Relationship, Drug; Female; Haemophilus Infections; Humans; Jurkat Cells; Male; Middle Aged; Signal Transduction; T-Lymphocytes; TOR Serine-Threonine Kinases

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

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Erythromycin; Haemophilus Infections; Humans; Japan; Macrolides; Male; Middle Aged; Prognosis; Sputum; Suppuration

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Bronchiolitis; Bronchiolitis Obliterans; Haemophilus Infections; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections

Topics: Adult; Aftercare; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Azithromycin; Bronchiolitis; CD4 Lymphocyte Count; Denmark; Dyspnea; Granulomatosis with Polyangiitis; HIV Infections; Humans; Malaysia; Male; Pneumonia, Pneumocystis; Prednisolone; Rare Diseases; Respiratory Function Tests; Sustained Virologic Response; Thailand; Tomography, X-Ray Computed; Treatment Outcome; Viral Load

Diffuse panbronchiolitis is a progressive fatal respiratory disease of unknown cause seen predominantly in Southeast Asian adults. We report this condition in a 10-year-old child of Korean birth because of the uncommon presentation at this age and the favorable outcome associated with early diagnosis. Our objective was also to demonstrate the gradual but complete resolution of the disease and sustained remission from early institution of azithromycin.

Topics: Anti-Bacterial Agents; Asian People; Azithromycin; Bronchiolitis; Child; Haemophilus Infections; Humans; Male

Interleukin-17 (IL-17) is involved in autoimmune and chronic pulmonary diseases and linked with neutrophilic inflammation. Azithromycin reduces and prevents broncholaveolar lavage (BAL) neutrophilia after lung transplantation (LTx). In this investigation we assessed the involvement of IL-17 in different post-transplant complications in human LTx biopsies.. Immunohistochemical staining against IL-17A was performed on biopsies of LTx patients with either chronic rejection, acute A-grade rejection (A > 2B0), lymphocytic bronchiolitis (LB), infection, and stable patients. Biopsies of 7 patients with LB were stained before and after azithromycin treatment. IL-17+ cells were quantified as number per square millimeter of lamina propria. Double staining with CD4/CD8 was performed to determine the origin of IL-17.. In the LB group, biopsies showed a significant presence of IL-17+ cells/mm2 of lamina propria compared with the stable, acute A-grade/chronic rejection and infection groups (p < 0.0001). The number of IL-17+ cells on biopsy correlated with percent BAL (%BAL) neutrophilia (r = 0.34, p = 0.0056). Azithromycin reduced both %BAL neutrophilia and IL-17+ cells (both p = 0.016) in the LB group. CD8+ cells were the major source of IL-17.. IL-17+ / CD8+ cells are present in LB after LTx but not in acute A-grade/chronic rejection nor during infection. Moreover, azithromycin significantly decreased the number of IL-17+ cells in the airway wall, which may further explain its effect on BAL neutrophilia.

Topics: Adult; Azithromycin; Bronchiolitis; Female; Humans; Interleukin-17; Lung Transplantation; Lymphocytes; Male; Middle Aged; Neutrophils; Postoperative Complications; Retrospective Studies

Macrolide antibiotics, like erythromycin, clarithromycin, and azithromycin, possess anti-inflammatory properties. These properties are considered fundamental to the efficacy of these three macrolides in the treatment of chronic inflammatory diseases like diffuse panbronchiolitis and cystic fibrosis. However, long-term treatment with macrolide antibiotics presents a considerable risk for promotion of bacterial resistance. We have examined antibacterial and anti-inflammatory effects of a novel macrolide class: N'-substituted 2'-O,3'-N-carbonimidoyl bridged erythromycin-derived 14- and 15-membered macrolides. A small focused library was prepared, and compounds without antimicrobial activity, which inhibited IL-6 production, were selected. Data analysis led to a statistical model that could be used for the design of novel anti-inflammatory macrolides. The most promising compound from this library retained the anti-inflammatory activity observed with azithromycin in lipopolysaccharide-induced pulmonary neutrophilia in vivo. Importantly, this study strongly suggests that antimicrobial and anti-inflammatory activities of macrolides are independent and can be separated, which raises development plausibility of novel anti-inflammatory therapeutics.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; Bronchiolitis; Bronchoalveolar Lavage Fluid; Cell Line; Clarithromycin; Cystic Fibrosis; Drug Interactions; Drug Resistance, Bacterial; Erythromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Interleukin-6; Lipopolysaccharides; Lung; Macrolides; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Moraxella catarrhalis; Neutrophils; Rats; Rats, Sprague-Dawley; Streptococcus

Acute rejection represents a major problem after organ transplantation, being a recognized risk for chronic rejection and mortality. Recently, it became clear that lymphocytic bronchiolitis (LB, B-grade acute rejection) is more important than previously thought, as it predisposes to chronic rejection. We aimed to verify whether daily fluctuations of air pollution, measured as particulate matter (PM) are related to histologically proven A-grade rejection and/or LB and bronchoalveolar lavage (BAL) fluid cellularity after lung transplantation. We fitted a mixed model to examine the association between daily variations in PM(10) and A-grade rejection/LB on 1276 bronchoscopic biopsies (397 patients, 416 transplantations) taken between 2001 and 2011. A difference of 10 μg/m(3) in PM(10) 3 days before diagnosis of LB was associated with an OR of 1.15 (95% CI 1.04-1.27; p = 0.0044) but not with A-grade rejection (OR = 1.05; 95% CI 0.95-1.15; p = 0.32). Variations in PM(10) at lag day 3 correlated with neutrophils (p = 0.013), lymphocytes (p = 0.0031) and total cell count (p = 0.024) in BAL. Importantly, we only found an effect of PM10 on LB in patients not taking azithromycin. LB predisposed to chronic rejection (p < 0.0001). The risk for LB after lung transplantation increased with temporal changes in particulate air pollution, and this was associated with BAL neutrophilia and lymphocytosis. Azithromycin was protective against this PM effect.

Topics: Adult; Air Pollution; Anti-Bacterial Agents; Azithromycin; Biopsy; Bronchiolitis; Humans; Lung Transplantation; Lymphocytes; Middle Aged; Prospective Studies

A 67-year-old never-smoker was diagnosed with diffuse panbronchiolitis (DPB) and was started on 250 mg azithromycin twice weekly. Over a 16-month observation period, lung function was assessed monthly, including a dedicated small airways test, the multiple breath nitrogen washout (MBW) with indices S(cond) and S(acin) of ventilation heterogeneity at the level of the conductive and acinar air spaces, respectively. Baseline measurements indicated moderate airway obstruction, air trapping and considerable dysfunction of the small airways around the acinar entrance. Treatment resulted in excellent symptomatic improvement paralleled by marked improvements in FEV(1), FVC, RV/TLC, S(cond) and S(acin); by contrast, there were no consistent changes in FEF(75) or TL(CO). While improvements were such that S(cond) fell within normal limits after 5 months, S(acin) remained abnormal even after 16 months of treatment. This suggests a distinct acinar structural abnormality in DPB that cannot be reversed by azithromycin.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Breath Tests; Bronchiolitis; Haemophilus Infections; Humans; Male; Nitrogen; Spirometry; Treatment Outcome

Patients with diffuse panbronchiolitis (DPB) are routinely treated with erythromycin, clarithromycin, and roxithromycin. The clinical effect of azithromycin on DPB has not been confirmed in a large cohort.. The present study was undertaken to investigate the clinical effects of azithromycin on patients with DPB.. Fifty-one patients with DPB treated with azithromycin in Shanghai Pulmonary Hospital, China, from July 2001 to April 2007 were analyzed retrospectively. Azithromycin (500 mg a day) was administrated intravenously in the first 1-2 weeks, taken orally (500 mg, once a day) for 3 months, and tapered to 3 times a week for 6-12 months. The patients were followed up until September 1, 2009. The therapeutic effect, according to their clinical and radiological findings, arterial gas analysis, lung function, and sputum bacterium before and after the therapy, was categorized into the following five grades: 1) cured; 2) improved; 3) no response; 4) aggravation, and 5) relapse.. With azithromycin therapy, 14 (27.5%) patients with DPB were completely cured. The symptoms were eliminated to certain degrees for the other 36 cases (70.6%) of DPB. Five-year survival in this cohort was 94.1%.. Azithromycin is effective and well tolerated for patients with diffuse panbronchiolitis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asian People; Azithromycin; Bronchiolitis; Child; Cohort Studies; Female; Follow-Up Studies; Haemophilus Infections; Humans; Male; Middle Aged; Retrospective Studies; Young Adult

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Female; Humans; Male; Middle Aged; Pseudomonas Infections; Treatment Outcome

Since "small-dose and long-term" administration of erythromycin (EM) was shown to be efficacious in the treatment of chronic respiratory disease, the modulation of host defense responses by EM has attracted much attention. Although there is considerable controversy, it was recently demonstrated that EM activity reduces neutrophil function. In this study, we investigated the in vitro effects of the macrolides erythromycin (EM), a 14-membered ring, azithromycin (AZM), a 15-membered ring and rokitamycin (RKM), a 16-membered ring macrolide, on neutrophil function. The DCFH-DA method and cytochrome C method were used for assay of active oxygen generation and the Boyden-chamber method was used for assay of chemotaxis. EM and AZM, both of which have been shown to be clinically effective in the treatment of Diffuse panbronchiolitis (DPB), significantly suppressed active oxygen generation and chemotaxis of neutrophils at low concentrations equivalent to therapeutic doses (0.5 approximately 1.0 microgram/ml, p < 0.05), whereas the clinically ineffective RKM did not. The in vitro inhibitory effects of EM and AZM on active oxygen generation and chemotaxis of neutrophils demonstrated in the present study may be responsible for the therapeutic efficacy of these 14-membered and 15-membered ring macrolides in the treatment of DPB patients.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Chemotaxis, Leukocyte; Erythromycin; Humans; Miocamycin; Neutrophil Activation; Neutrophils

Pseudomonas aeruginosa is a saprophyte opportunistic bacteria which frequently colonizes the respiratory tract of patients presenting a severe chronic bronchitis pathology. Secreting a number of exotoxins and enzymes inducing an inflammation and necrosing of the surrounding tissues, it provokes irreversible pulmonary lesions. Different experimental in vitro works evidenced macrolides activity on the production and/or secretion of these factors, with a diminution of elastase, protease, lecithinase and D-nase synthesis. Among the macrolides, azithromycin seems to have the most pronounced activity. In vivo, some patients suffering from bronchiolitis or cystic fibrosis have been clinically improved with a treatment using erythromycin, or clarithromycin or azithromycin. These very preliminary results demand to be confirmed but the macrolides could allow a decrease of Pseudomonas aeruginosa pathogenicity and thus stop the deterioration of pulmonary functions.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Cystic Fibrosis; Humans; In Vitro Techniques; Pseudomonas aeruginosa; Pseudomonas Infections; Virulence