pulmicort and Pulmonary-Eosinophilia

In rare cases, cutaneous larva migrans may be complicated by Löffler syndrome. This syndrome is thought to result from a type I hypersensitivity reaction related to the pulmonary larval migration phase of various parasites. It is characterized by migratory pulmonary eosinophilic infiltrates and peripheral eosinophilia, with malaise, fever, and cough. Our patient was successfully treated with ivermectin, a corticosteroid cream, and inhalation medication in an early phase, which prevented complications. We present the details of this case and review the literature.

Topics: Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Antiparasitic Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Clobetasol; Drug Combinations; Ethanolamines; Humans; Ivermectin; Larva Migrans; Male; Pulmonary Eosinophilia

Budesonide at 800 μg/d is generally suggested for treatment of nonasthmatic eosinophilic bronchitis (NAEB). In asthma, adjunctive therapy with montelukast has been shown to confer addictive anti-inflammatory effects to inhaled corticosteroid (ICS). However, whether such effects could be extrapolated to NAEB is not known.. To study the efficacy and tolerability of add-on therapy with montelukast as compared to double-dose ICS in suppressing airway eosinophilia and decreasing cough severity in NAEB.. In a randomized controlled trial, 26 nonsmoking, steroid-naïve NAEB patients presenting with chronic cough were treated with 800 μg/d budesonide or 400 μg/d budesonide plus montelukast 10 mg/d for 4 weeks. Cough visual analogue scale (CVAS) and eosinophil differential ratio in induced sputum (Eos) were monitored at baseline, Week 1, 2 and 4. Adverse events during treatment were recorded.. The two groups were comparable in age, gender distribution, cough duration, FEV(1)% predicted, FEV(1)/FEV ratio, baseline CVAS and geometric mean of Eos. Both regimens significantly reduced Eos and CVAS throughout the treatment course, with abrogation of sputum eosinophilia at end of therapy. There was no significant difference between the two groups in reduction of Eos and CVAS at all time points. Both regimens were well tolerated.. This preliminary study demonstrated that add-on montelukast might be an effective and well tolerated alternative to the generally suggested dose of ICS in treating steroid-naive NAEB, with suppression of eosinophilic inflammation, reduction of cough severity and sparing of ICS doses. (NCT01121016).

Topics: Acetates; Adult; Aged; Bronchitis; Bronchodilator Agents; Budesonide; Chronic Disease; Cough; Cyclopropanes; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Middle Aged; Pilot Projects; Pulmonary Eosinophilia; Quinolines; Sulfides; Treatment Outcome; Young Adult

This study is an extended follow-up for 24 months of a 12-week trial to study the long-term clinical efficacy of low-dose inhaled budesonide (BUD) once or twice daily in children with mild asthma. A total of 122 children (mean age 9.7 years, girls/boys; 42/80) with mild asthma (FEV1 103.7% of predicted, reversibility in FEV1 3.5%, and fall in FEV1 after exercise 12.2%), not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. The children were treated with inhaled BUD 100 or 200 microg administered via Turbuhaler once daily in the morning, 100 microg twice daily, or placebo for 27 months. Exercise and methacholine challenges were performed at 3-month intervals the first year and at 6-month intervals the second year, in a total of seven visits. A significant dose-response effect favoring BUD 200 microg daily (vs 100 microg daily) was found when comparing changes in FEV1, FEF25%, and FEV50%; the fall in FEV1 after an exercise test; and the effect on blood eosinophils. Bronchial hyperreactivity to methacholine decreased significantly on three visits in patients treated with BUD 200 microg daily compared to placebo. Growth rate was not significantly affected except in children aged 7-11 years at baseline after 12 months of treatment. In conclusion, 100 or 200 microg daily of inhaled BUD for 27 months is safe and effective in protecting against exercise-induced asthma and achieving nearly normal lung function. Baseline lung function was not significantly affected in this group of children with mild asthma.

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents; Asthma; Blood Proteins; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Eosinophil Granule Proteins; Eosinophils; Exercise Test; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Patient Compliance; Placebos; Pulmonary Eosinophilia; Ribonucleases

This study aims to explore the potential of. Using flow cytometry, we enumerated sputum and blood HPCs and EoPs in patients with NAEB (n=15), EA (n=15), and HC (n=14) at baseline. Patients with NAEB and EA were then treated for 1 month with budesonide (200 μg, bid) or budesonide and formoterol (200/6 μg, bid), respectively. HPCs and EoPs in both compartments were re-evaluated.. At baseline, NAEB and EA both had significantly greater numbers of sputum but not blood HPCs and EoPs (. NAEB patients have increased airway levels of HPCs and EoPs. One-month treatment with ICS did not fully suppress the level of EoPs in NAEB. Controlling

Topics: Adrenal Cortex Hormones; Asthma; Bronchitis; Budesonide; Eosinophils; Humans; Pulmonary Eosinophilia

Mesalazine suppositories are widely used to treat ulcerative colitis and have a guaranteed safety profile, but although rare, they can cause pulmonary toxicity. A 35-year-old woman with ulcerative colitis was diagnosed to have acute eosinophilic pneumonia after 29 days of oral mesalazine use and improved after mesalazine and corticosteroid were withdrawn. Reintroduction of mesalazine suppositories resulted in acute eosinophilic pneumonia recurrence after 28 days. Mesalazine re-administration (even via a different route) in patients with a history of mesalazine-induced eosinophilic pneumonia should be undertaken cautiously, because eosinophilic pneumonia may recurrence.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Colonoscopy; Female; Humans; Mesalamine; Methylprednisolone; Pneumonia; Probiotics; Pulmonary Eosinophilia; Recurrence; Thorax; Tomography, X-Ray Computed

Phosphodiesterase 4 (PDE4) is a key cAMP-metabolizing enzyme involved in the pathogenesis of inflammatory disease, and its pharmacological inhibition has been shown to exert therapeutic efficacy in chronic obstructive pulmonary disease (COPD). Herein, we describe a drug discovery program aiming at the identification of novel classes of potent PDE4 inhibitors suitable for pulmonary administration. Starting from a previous series of benzoic acid esters, we explored the chemical space in the solvent-exposed region of the enzyme catalytic binding pocket. Extensive structural modifications led to the discovery of a number of heterocycloalkyl esters as potent in vitro PDE4 inhibitors. (S*,S**)-18e and (S*,S**)-22e, in particular, exhibited optimal in vitro ADME and pharmacokinetics properties and dose-dependently counteracted acute lung eosinophilia in an experimental animal model. The optimal biological profile as well as the excellent solid-state properties suggest that both compounds have the potential to be effective topical agents for treating respiratory inflammatory diseases.

Topics: Administration, Inhalation; Animals; Binding Sites; Cyclic Nucleotide Phosphodiesterases, Type 4; Dose-Response Relationship, Drug; Drug Discovery; Drug Evaluation, Preclinical; Drug Stability; Humans; Male; Phosphodiesterase 4 Inhibitors; Pulmonary Eosinophilia; Pyrrolidines; Rats, Inbred BN; Respiratory Tract Diseases; Structure-Activity Relationship; Thiazoles

Allergic asthma is strongly associated with the exposure to house dust mite (HDM) and is characterized by eosinophilic pulmonary inflammation and airway hyperresponsiveness (AHR). Recently, there is an increased interest in using dietary oligosaccharides, also known as prebiotics, as a novel strategy to prevent the development of, or reduce, symptoms of allergy.. We investigated the preventive capacity of dietary galacto-oligosaccharides (GOS) compared to an intra-airway therapeutic treatment with budesonide on the development of HDM-induced allergic asthma in mice.. BALB/c mice were intranasally sensitized with 1 μg HDM on day 0 followed by daily intranasal challenge with PBS or 10 μg HDM on days 7 to 11. Two weeks prior to the first sensitization and throughout the experiment mice were fed a control diet or a diet containing 1% GOS. Reference mice were oropharyngeally instilled with budesonide (500 μg/kg) on days 7, 9, 11, and 13, while being fed the control diet. On day 14, AHR was measured by nebulizing increasing doses of methacholine into the airways. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lungs were collected.. Sensitization and challenge with HDM resulted in AHR. In contrast to budesonide, dietary intervention with 1% GOS prevented the development of AHR. HDM sensitization and challenge resulted in a significant increase in BALF leukocytes numbers, which was suppressed by budesonide treatment and dietary intervention with 1% GOS. Moreover, HDM sensitization and challenge resulted in significantly enhanced concentrations of IL-6, CCL17, IL-33, CCL5 and IL-13 in lung tissue. Both dietary intervention with 1% GOS or budesonide treatment significantly decreased the HDM-induced increased concentrations of CCL5 and IL-13 in lung tissue, while budesonide also reduced the HDM-enhanced concentrations of IL-6 and CCL17 in lung tissue.. Not only did dietary intervention with 1% GOS during sensitization and challenge prevent the induction of airway eosinophilia and Th2-related cytokine and chemokine concentrations in the lung equally effective as budesonide treatment, it also prevented AHR development in HDM-allergic mice. GOS might be useful for the prevention and/or treatment of symptoms in asthmatic disease.

Topics: Animals; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Bronchodilator Agents; Budesonide; Cytokines; Dietary Carbohydrates; Disease Models, Animal; Galactosides; Lung; Male; Mice, Inbred BALB C; Oligosaccharides; Prebiotics; Pulmonary Eosinophilia; Pyroglyphidae; Th2 Cells

Topics: Adult; Breath Tests; Bronchial Provocation Tests; Bronchitis; Budesonide; Cupressus; Female; Humans; Immunoglobulin E; Male; Nitric Oxide; Pulmonary Eosinophilia; Rhinitis, Allergic, Seasonal; Skin Tests; Sputum

Intratracheal instillation of Sephadex particles is a convenient model for assessing the impact of potential anti-inflammatory compounds on lung eosinophilia thought to be a key feature in asthma pathophysiology. However, the underlying cellular and molecular mechanisms involved are poorly understood. We have studied the time course of Sephadex-induced lung eosinophilia, changes in pulmonary T cell numbers, and gene and protein expression as well as the immunological and pharmacological modulation of these inflammatory indices in the Sprague Dawley rat. Sephadex increased T cell numbers (including CD4(+) T cells) and evoked a pulmonary eosinophilia that was associated with an increase in gene/protein expression of the Th2-type cytokines IL-4, IL-5, and IL-13 and eotaxin in lung tissue. Sephadex instillation also induced airway hyperreactivity to acetylcholine and bradykinin. A neutralizing Ab (R73) against the alphabeta-TCR caused 54% depletion of total (CD2(+)) pulmonary T cells accompanied by a significant inhibition of IL-4, IL-13 and eotaxin gene expression together with suppression (65% inhibition) of eosinophils in lung tissue 24 h after Sephadex treatment. Sephadex-induced eosinophilia and Th2 cytokine gene and/or protein expression were sensitive to cyclosporin A and budesonide, compounds that inhibit T cell function, suggesting a pivotal role for T cells in orchestrating Sephadex-induced inflammation in this model.

Topics: Acetylcholine; Animals; Antibodies, Monoclonal; Biomarkers; Bradykinin; Bronchial Hyperreactivity; Budesonide; Cell Movement; Cells, Cultured; Cyclosporine; Cytokines; Dextrans; Gene Expression Regulation; Inflammation; Interleukin-2; Intubation, Intratracheal; Lung; Lymphocyte Depletion; Male; Mast Cells; Pulmonary Eosinophilia; Rats; Rats, Sprague-Dawley; T-Lymphocyte Subsets; Time Factors

A detailed analysis has been carried out of the correlation between the signals detected by MRI in the rat lung after allergen or endotoxin challenge and parameters of inflammation determined in the broncho-alveolar lavage (BAL) fluid. MRI signals after allergen correlated highly significantly with the BAL fluid eosinophil number, eosinophil peroxidase activity and protein concentration. Similar highly significant correlations were seen when the anti-inflammatory glucocorticosteroid, budesonide, manifested against allergen. In contrast, following endotoxin challenge, mucus was the sole BAL fluid parameter that correlated significantly with the long lasting signal detected by MRI. Since edema is an integral component of pulmonary inflammation, MRI provides a noninvasive means of monitoring the course of the inflammatory response and should prove invaluable in profiling anti-inflammatory drugs in vivo. Further, the prospect of noninvasively detecting a sustained mucus hypersecretory phenotype in the lung brings an important new perspective to models of chronic obstructive pulmonary diseases.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Asthma; Bronchoalveolar Lavage Fluid; Budesonide; Eosinophil Peroxidase; Inflammation; Lipopolysaccharides; Lung; Magnetic Resonance Imaging; Male; Mucus; Ovalbumin; Peroxidases; Pulmonary Disease, Chronic Obstructive; Pulmonary Edema; Pulmonary Eosinophilia; Rats; Rats, Inbred BN; Respiration

Spontaneous or steroid-induced eosinophil apoptosis occurring in vitro has not been demonstrated in lung tissues in vivo. This study examines cell apoptosis in rat lungs using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) technique and transmission electron microscopy (TEM). After establishing sustained lung edema and eosinophilia by challenge with Sephadex beads intratracheally, budesonide treatment was started intratracheally. Sephadex alone increased the total number of apoptotic cells, which were not efficiently engulfed by macrophages or other cells, in vivo. Yet apoptotic tissue eosinophils were exceedingly rare (1 of 360 TEM-analyzed eosinophils). By contrast, approximately 20% of eosinophils in the airway lumen were apoptotic, and unengulfed. Budesonide promptly inhibited edema but 3 d of steroid treatment were required to reduce the established tissue eosinophilia. Not at any time point did budesonide induce eosinophil apoptosis (0 of 318 TEM-analyzed tissue eosinophils). We conclude that (1) eosinophil apoptosis can occur but is a rare event in vivo in respiratory tract tissues; (2) airway tissue eosinophils, rather than undergoing apoptosis, are eliminated by migration into airway lumen followed by apoptosis and mucociliary clearance; (3) anti-inflammatory steroid treatment may not increase eosinophil apoptosis in vivo nor may it affect the luminal entry of eosinophils; (4) steroids permit elimination of eosinophils into airway lumen and slowly resolve established lung eosinophilia.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Bronchoalveolar Lavage Fluid; Budesonide; Dextrans; Disease Models, Animal; Drug Evaluation, Preclinical; In Situ Nick-End Labeling; Inflammation; Leukocyte Count; Male; Microscopy, Electron, Scanning Transmission; Mucociliary Clearance; Pulmonary Edema; Pulmonary Eosinophilia; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

We report a case of typical chronic eosinophilic pneumonia (CEP), in a female of 27 years-old suffering bronchial asthma light. Although the initial answer to the treatment with steroids was satisfactory, the patient develop difficult to control asthma (DCA). DCA is a clinical situation which requires careful investigation of several potential factors which can be solved. We suggest a protocol of treatment for patients affected with DCA.

Topics: Administration, Topical; Adult; Aerosols; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Chronic Disease; Female; Glucocorticoids; Humans; Pregnenediones; Pulmonary Eosinophilia; Radiography, Thoracic

Topical corticosteroids are effective in the treatment of asthma by improving bronchial hyperresponsiveness and reducing airway inflammation.. We assessed the effect of a nebulized corticosteroid, budesonide, on airway hyperresponsiveness and inflammatory response provoked by inhalation of trimellitic anhydride (TMA) dust, a known cause of occupational asthma in human beings, in guinea pigs sensitized to the free hapten. Male Dunkin-Hartley guinea pigs (n = 24) were injected intradermally with 0.1 ml of 0.3% TMA in corn oil, followed by exposure 21 to 28 days later to five consecutive doses of budesonide aerosol (0.5 mg/ml) or saline solution, administered for 10 minutes every 12 hours. They were then exposed (noses only) to TMA dust (8 mg/m3) or air for 1 hour (four groups, n = 6 in each). Airway responsiveness to acetylcholine, defined as the concentration needed to cause a 200% increase in lung resistance (PC200), was measured 8 hours later.. In saline-treated guinea pigs exposed to TMA, mean PC200 was 0.094 mmol/L (geometric SEM, 1.4 mmol/L) compared with 0.31 mmol/L (geometric SEM, 1.3 mmol/L, p < 0.05) in those guinea pigs pretreated with budesonide. In sham-exposed sensitized guinea pigs, PC200 was 0.35 mmol/L (geometric SEM, 1.2 mmol/L), which was not significantly different from the budesonide-treated group (0.36 mmol/L; geometric SEM, 1.3 mmol/L). There was a significant increase in the number of eosinophils in the subepithelium of guinea pigs further exposed to TMA dust (71.5 +/- 6.8 cells/unit area [mean +/- SEM]) compared with those exposed to air (22.7 +/- 6.7, p < 0.01). Budesonide did not inhibit the number of subepithelial eosinophils of guinea pigs exposed to TMA dust (54.0 +/- 3.7 cells/unit area) or in those exposed to air (24.3 +/- 6.7 cells/unit area) and did not affect the increase in eosinophils found in bronchoalveolar fluid.. Budesonide significantly inhibited the increase in airway responsiveness but not the eosinophilic inflammation induced by exposure to TMA dust in sensitized guinea pigs.

Topics: Administration, Topical; Aerosols; Analysis of Variance; Animals; Anti-Inflammatory Agents; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Glucocorticoids; Guinea Pigs; Male; Phthalic Anhydrides; Pregnenediones; Pulmonary Eosinophilia; Respiratory Hypersensitivity