Effects of azithromycin on bronchial remodeling in the natural model of severe neutrophilic asthma in horses

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.

Short-Term Acute Exposure to Wildfire Smoke and Lung Function among Royal Canadian Mounted Police (RCMP) Officers

The increasing incidence of extreme wildfire is becoming a concern for public health. Although long-term exposure to wildfire smoke is associated with respiratory illnesses, reports on the association between short-term occupational exposure to wildfire smoke and lung function remain scarce. In this cross-sectional study, we analyzed data from 218 Royal Canadian Mounted Police officers (mean age: 38 ± 9 years) deployed at the Fort McMurray wildfires in 2016. Individual exposure to air pollutants was calculated by integrating the duration of exposure with the air quality parameters obtained from the nearest air quality monitoring station during the phase of deployment. Lung function was measured using spirometry and body plethysmography. Association between exposure and lung function was examined using principal component linear regression analysis, adjusting for potential confounders. In our findings, the participants were predominantly male (71%). Mean forced expiratory volume in 1 s (FEV1), and residual volume (RV) were 76.5 ± 5.9 and 80.1 ± 19.5 (% predicted). A marginal association was observed between air pollution and higher RV [β: 1.55; 95% CI: −0.28 to 3.37 per interquartile change of air pollution index], but not with other lung function indices. The association between air pollution index and RV was significantly higher in participants who were screened within the first three months of deployment (2.80; 0.91 to 4.70) than those screened later (−0.28; −2.58 to 2.03), indicating a stronger effect of air pollution on peripheral airways. Acute short-term exposure to wildfire-associated air pollutants may impose subtle but clinically important deleterious respiratory effects, particularly in the peripheral airways.

Clinical implications of concentration of alveolar nitric oxide in asthmatic and non-asthmatic subacute cough

Background and objective: Asthma is one of the important causes of subacute cough. Concentration of alveolar nitric oxide (CANO) is a sensitive inflammatory indicator of peripheral airways, which has received much less attention than fraction of exhaled nitric oxide (FeNO50). The main objective of this study was to explore the correlation between CANO and clinical parameters in asthmatic and non-asthmatic subacute cough, which might promote understanding the clinical utility of CANO in these special patient population. Materials and methods: 155 patients with subacute cough were included consecutively, of which 25 were diagnosed as asthma. Data for demographic characteristics, FeNO50, CANO, baseline spirometry, bronchial provocation test (or bronchodilation test) and response dose ratio (RDR) was collected. Differences between asthmatic and non-asthmatic group were analyzed. Spearman’s correlation coefficient (rho) was used to evaluate the correlation between FeNO50, CANO and other clinical parameters. Results: In patients with subacute cough, baseline CANO values did not differ between asthmatic and non-asthmatic patients (4.4(1.3, 11.4) versus 4.0(2.1, 6.8) ppb, P>0.05). Besides, CANO exhibited stronger association with pulmonary function parameters when compared with FeNO50. For asthmatic subacute cough, CANO was inversely correlated with FEV1/FVC (rho=-0.69, P<0.01) and small airway parameters including MEF25 (rho=-0.47, P<0.05) and MMEF (rho=-0.45, P<0.05). For non-asthmatic subacute cough, CANO was inversely correlated with MEF25 (rho=-0.19, P<0.05) and RDR (rho=-0.21, P<0.05). Conclusion: In subacute cough, asthmatic and non-asthmatic patients had similar values of baseline CANO. In both asthmatic and non-asthmatic subacute cough, CANO exhibited stronger association with pulmonary function parameters when compared with FeNO50. A low CANO value in non-asthmatic subacute cough corresponded to a higher value of RDR, which implied stronger tendency towards airway responsiveness.

Bronchial hygiene technique in patients with cystic fibrosis

Cystic Fibrosis is characterized by excess pulmonary secretions that cause recurrent respiratory infections, with consequent deterioration of gas exchange. Bronchial hygiene techniques aim to mobilize secretions from the peripheral airways so that they can be eliminated by coughing or tracheal aspiration. To identify the effects of different bronchial hygiene techniques on improving lung function in patients with Cystic Fibrosis. Through a systematic review of the literature, randomized controlled trials (RCTs) published between 2007 and 2021 were selected, according to the highest score in the PEDro score. The search involved the PEDro and PubMed databases, using the following keywords: bronchial hygiene. Six ECR`s were included. One study performedthe techniques during anesthesia and observed increased resistance and reduced compliance. Regarding FEV1, 3 RCTs with hospitalized patients showed improvement in lung function, regardless of the technique used. In outpatients, there was no improvement. Regarding secretion weight, the cough machine produced more secretion than autogenous drainage, as well as a drop in saturation after the 2-min walk test, and increased FEV1. Bronchial hygiene techniques in patients with cystic fibrosis have been shown to be effective in removing mucus, with consequent improvement in lung function and aerobic fitness.

Extrafine HFA-beclomethasone-formoterol vs. nonextrafine combination of an inhaled corticosteroid and a long acting β2-agonist in patients with persistent asthma: A systematic review and meta-analysis

Objective Airway inflammation in asthma involves not only the central airways but extends to peripheral airways. Lung deposition may be key for an appropriate treatment of asthma. We compared the clinical effects of extrafine hydrofluoroalkane (HFA)-beclomethasone-formoterol (BDP-F) versus equipotent doses of nonextrafine combination of an inhaled corticosteroid and a long acting β2-agonist (ICS-LABA) in asthma. Methods We identified eligible studies by a comprehensive literature search of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). Data analysis was performed with the Review Manager 5.3.5 software (Cochrane IMS, 2014). Results A total of 2326 patients with asthma from ten published randomized controlled trials (RCTs) were enrolled for analysis. Change from baseline in morning pre-dose peak expiratory flow (PEF), evening pre-dose PEF and forced expiratory volume in one second (FEV1) were detected no significant differences between extrafine HFA-BDP-F and nonextrafine ICS-LABAs (p = 0.23, p = 0.99 and p = 0.23, respectively). Extrafine HFA-BDP-F did not show any greater benefit in forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%), the parameter concerning peripheral airways (MD 0.03L/s, p = 0.65; n = 877). There were no substantial differences between interventions in fractional exhaled nitric oxide (FeNO) levels or in its alveolar fraction. The overall analysis showed no significant benefit of extrafine HFA-BDP-F over nonextrafine ICS-LABA in improving Asthma Control Test (ACT) score (p = 0.30) or decreasing the number of puffs of rescue medication use (p = 0.16). Extrafine HFA-BDP-F did not lead to less exacerbations than nonextrafine ICS-LABA (RR 0.61, 95% CI: 0.31 to 1.20; I2 = 0; p = 0.15). Conclusion Enrolled RCTs of extrafine HFA-BDP-F have demonstrated no significant advantages over the equivalent combination of nonextrafine ICS-LABA in improving pulmonary function concerning central airways or peripheral airways, improving asthma symptom control or reducing exacerbation rate.

Intrapleural Foreign Body: Case Report

The detection of foreign bodies in the pleural cavity is rare and mostly consequent to iatrogenic or traumatic events. The migration of an inhaled foreign body from the airways to the pleural space through a bronchopleural fistula is an exceptional event. We report a case of a pleural empyema consequent to an inhaled wooden skewer. CT scan and bronchoscopy were unable to identify the foreign body, due to its migration in the peripheral airways. The thin and pointed foreign body perforated the visceral pleural surface emerging in the pleural cavity.

EVALUATION OF SMALL AIRWAY REVERSIBILITY AMONG ASTHMATIC PATIENTS WITH NON-OBSTRUCTIVE PATTERNS OF SPIROMETRY

Background: Although the forced expiratory flow parameters are increasingly used in the diagnosis of small airway disease (SAD), the reversibility of these indicators is rarely described. The aim of this study is to evaluate the association of small airways reversibility with the presence of SAD and bronchodilator reversibility (BDR) of the proximal airways. Methods: The forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the indicators of SAD (FEF25%, FEF50%, FEF75%, FEF25-75%, and FEF75-85%) were measured before and 20 minutes after salbutamol administration (200 mcg by using inhaler/Spacer). Positive BDR was accepted when FEV1 or FVC was increased ? 12% and > 200 ml, indicating responsive proximal airways. Positive small airway reversibility was diagnosed when any of the small airway indicators is increased ? 30% above the baseline results. All measurements were performed with the All-flow spirometer (Clement Clarke International, Harlow, UK). Results: Evidence of SAD was found in 62.1% of all participants and in 75.2% of those who showed responsive proximal airways. The positive predictive value of the SAD in diagnosing responsive proximal airways was 67.8%. The reversibility of the small airway indicators showed insignificant association with the FEV1 or FVC BDR. The reversibility of FEF50%, FEF75% and FEF25-75% showed significant association with the diagnosis of SAD, with specificities ranging from 75.5%-81.1%. Conclusion: SAD has a significant association with positive reversibility of both the proximal and the peripheral airways. Further studies are needed to evaluate the clinical significance of positive small airway reversibility in the diagnosis and management of obstructive lung diseases. Keywords: Asthma; Small airway disease; Bronchodilator Reversibility, FEV1, FVC; FEF25-75%

Short-term acute exposure to wildfire smoke and lung function in a Royal Canadian Mounted Police (RCMP) cohort

ABSTRACTRationaleThe increasing incidence of extreme wildfire is becoming a concern for public health. Although long-term exposure to wildfire smoke is associated with respiratory illnesses, reports on the association between short-term occupational exposure to wildfire smoke and lung function remain scarce.MethodsIn this cross-sectional study, we analyzed data of 218 Royal Canadian Mounted Police officers (mean age: 38±9 years) deployed at the Fort McMurray wildfire in 2016. Individual exposure to air pollutants was calculated by integrating the duration of exposure with the air quality parameters obtained from the nearest air quality monitoring station during the phase of deployment. Lung function was measured using spirometry and body plethysmography. Association between exposure and lung function was examined using principal component linear regression analysis, adjusting for potential confounders.ResultsThe participants were predominantly male (71%). Mean forced expiratory volume in 1 second (FEV1), and residual volume (RV) were 76.5±5.9 and 80.1±19.5 of % predicted. A marginal association was observed between the principal air pollution component and higher RV [β: 1.55; 95%CI: -0.28 to 3.37 per interquartile range change of air pollution index], but not with other lung function indices. The association was significantly higher in participants who were screened within the first three months of deployment [2.80; 0.91 to 4.70] than those screened later [-0.28; -2.58 to 2.03], indicating a more acute effect of air pollution on peripheral airways.ConclusionAcute short-term exposure to wildfire-associated air pollutants may impose subtle but clinically important deleterious respiratory effects, particularly in the peripheral airways.