CLINICAL PROFILE OF ASTHMA IN MALE SMOKERS

Introduction: st Asthma is traditionally dened as a functional abnormality with reversibility in forced expiratory volume in 1 second of more than 15% as opposed to irreversible or xed airway limitation in chronic obstructive pulmonary disease (COPD).This study aims to the assess the clinical symptoms, physical ndings and laboratory results in smoker patients reporting with symptoms suggestive of bronchial asthma . Material and method: This study was conducted in department of Respiratory Medicine of National institute of Medical sciences and research, Jaipur on 50 outdoor male smokers presented with respiratory complaints during period of September 2020 to May 2021. Result: 100 patients enrolled in this study. And 50 patients were diagnosed as bronchial asthma on the basis of steroid trial. Mean age of patients in our study is 48.00+10.41. Shortness of breath (48%) was the commonest complaint followed by cough(24%), expectoration (20%) and last was chest pain (8%). There were more current smokers (48%) followed by ex smokers (32%0 and least were reformed (20%).The most common symptoms in past history of patient was seasonal variation (96%) followed by eye itching (32%), chest tightness (60%), sneezing (56%), dust allergy(32%), non respiratory allergy and wheeze (24%) and last was positive family history of asthma or allergy. Past history showed different variation in which any one symptoms was present in 100% of patients, followed by 2 symptoms (95%), 3 symptoms (84%) and 4 symptoms (52%). Conclusion: This study concludes that presence of any two of the above described past symptoms or variables suggestive of asthma in past are diagnostic of asthma in smoker patients even in the presence of irreversible or partially reversible airway obstruction

Virus-Induced Asthma/Wheeze in Preschool Children: Longitudinal Assessment of Airflow Limitation Using Impulse Oscillometry

Several researchers have assessed the utility of Impulse Oscillometry System (IOS) in diagnosing and evaluating the severity of respiratory diseases in childhood, but none has investigated the impact of the fluctuations of IOS parameters in an individualized manner. In this two-year prospective study, we aimed to longitudinally evaluate changes in airflow limitation and bronchodilator responsiveness in steroid-naïve four- to six-year-old children during a virus-induced wheezing episode, with IOS pulmonary resistance parameters set at 5 (R5) and 20 (R20) Hz. Moreover, feasibility and reproducibility, in addition to the diagnostic properties of these parameters were examined. Lung function was assessed every six weeks (baseline), within the first 48 h following an acute wheezing episode (Day 0), after 10, and after 30 days. Forty-three out of 93 recruited children (4.5 ± 0.4 years old) experienced a wheezing episode during the study period. All children were able to perform the IOS effort in an acceptable and highly reproducible manner. R5 and R20 fluctuated independently of atopy, age, height, and weight. On Day 0, R5 values were significantly lower than the respective baseline values and returned to individual baseline levels within 10 days. Post-bronchodilation R5 values were similar to the baseline ones, reflecting a reversible airway obstruction on Day 0. Response to bronchodilation (ΔR5) was significantly more pronounced on Day 0. ΔR5 values lower than −20.5% had a sensitivity of 70% and a specificity of 76% and could accurately identify up to 75% of the examined preschoolers. This study provides evidence in favor of the objective utility of IOS as an easy, highly reproducible, and sensitive technique to assess clinically significant fluctuations and bronchodilation responses suggestive of airflow limitation. Reference values although necessary are suboptimal, utilizing the personal best values as personal reference is useful and reliable.

Cross-sectional study of reversible airway obstruction in LAM: better evidence is needed for bronchodilator and inhaled steroid use

Lymphangioleiomyomatosis can be associated with reversible airflow obstruction and although no guidelines around reversibility testing or inhaled therapy exist, many patients receive bronchodilators and inhaled corticosteroids. To better identify those who may benefit, we examined bronchodilator reversibility and inhaled therapy in a national cohort of 213 subjects. 20% of those tested had airway reversibility by standard criteria. 55% of patients used 13 different combinations of bronchodilators and inhaled corticosteroids. Increasing inhaler classes were associated with reversibility and more rapid FEV1 decline. Reversibility testing should be performed in all patients and inhaled therapy should be formally studied.

Potential Mechanisms of T Cell-Mediated and Eosinophil-Independent Bronchial Hyperresponsiveness

Bronchial asthma is a chronic disease characterized by reversible airway obstruction, mucus production, and bronchial hyperresponsiveness (BHR). Although Th2 cell-mediated eosinophilic inflammation is an important disease mechanism in the majority of patients with bronchial asthma, recent studies suggest the possible development of Th2-independent airway inflammation and BHR. These non-Th2 endotype patients seem to consist of multiple subgroups, and often do not respond to inhaled corticosteroids. Therefore, to understand the pathogenesis of asthma, it is important to characterize these non-Th2 subgroups. Recently, we demonstrated that Th9 cells induce eosinophil infiltration and eosinophil-independent BHR, and Th9 cells-mediated BHR may be resistant to glucocorticoid. In this review, we summarize the contribution of several T cell subsets in the development of bronchial asthma and introduce our recent study demonstrating Th9 cell-mediated and eosinophil-independent BHR.

Predictors of reversible airway obstruction with omalizumab in severe asthma: a real-life study

Background: Omalizumab may modulate airway remodeling in severe asthma. Using forced expiratory volume in 1 second (FEV1) as a surrogate of airway remodeling, we aimed to investigate if an omalizumab add-on in severe allergic asthma may lead to a persistent reversal of airway obstruction and to evaluate the potential biomarkers of airway obstruction reversibility. Methods: Data were collected before (T0) and after omalizumab add-on for 1 year (T1, 32 patients), 2 years (T2, 26 patients) and 4 years (T4, 13 patients). All patients had baseline FEV1 below 80 % predicted (60.5 ± 12.5 %). After omalizumab, 18 patients showed FEV1 normalization (reversible airway obstruction; RAO+) already at T1 (88.7 ± 14.9 %, p < 0.0001) that persisted up to T4 (83.2 ± 7.9, p < 0.01), while 14 patients (RAO−) had FEV1 persistently decreased, from T1 (65.2 ± 8.4%, p < 0.05) up to T4 (61.4 ± 6.2%, not significant). Both groups had significant improvement of symptoms and exacerbations after omalizumab at T1, which persisted up to T4. The comparison between pretreatment characteristics of the two groups showed that RAO+ patients, had higher values of circulating eosinophils, exhaled nitric oxide (FENO), prevalence of rhinitis and nasal polyps, need of oral corticosteroids, shorter asthma duration, higher FEV1 and response to albuterol test. The optimal cut-off points predicting FEV1 normalization after omalizumab add-on were 30.5 ppb for FENO and 305 cells/µl for eosinophils. Conclusions: This study suggests that omalizumab add-on contributes to the persistent reversal of airway obstruction in a consistent number of patients with severe allergic asthma, and this beneficial effect is predicted by elevated pretreatment FENO and circulating eosinophils.

Basophils trigger emphysema development in a murine model of COPD through IL-4–mediated generation of MMP-12–producing macrophages

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has generally been considered a non-Th2-type lung disorder, characterized by progressive airflow limitation with inflammation and emphysema, but its cellular and molecular mechanism remains ill defined, compared with that of asthma characterized by reversible airway obstruction. Here we show a previously unappreciated role for basophils at the initiation phase of emphysema formation in an elastase-induced murine model of COPD in that basophils represent less than 1% of lung-infiltrating cells. Intranasal elastase instillation elicited the recruitment of monocytes to the lung, followed by differentiation into interstitial macrophages (IMs) but rarely alveolar macrophages (AMs). Matrix metalloproteinase-12 (MMP-12) contributing to emphysema formation was highly expressed by IMs rather than AMs, in contrast to the prevailing assumption. Experiments using a series of genetically engineered mice suggested that basophil-derived IL-4, a Th2 cytokine, acted on lung-infiltrating monocytes to promote their differentiation into MMP-12–producing IMs that resulted in the destruction of alveolar walls and led to emphysema development. Indeed, mice deficient for IL-4 only in basophils failed to generate pathogenic MMP-12–producing IMs and hence develop emphysema. Thus, the basophil-derived IL-4/monocyte–derived IM/MMP-12 axis plays a crucial role in emphysema formation and therefore may be a potential target to slow down emphysema progression at the initiation phase of COPD.

Better understanding of childhood asthma, towards primary prevention – are we there yet? Consideration of pertinent literature

Asthma is a chronic disease, characterized by reversible airway obstruction, airway inflammation and hyper-reactivity. The prevalence of asthma has risen dramatically over the past decade, affecting around 300,000,000 people. The etiology is multifactorial, with genetic, epigenetic, developmental and environmental factors playing a role. A complex interaction between the intrauterine environment, the developing immune system, the infant's microbiome and infectious organisms may lead to the development of allergic sensitization and asthma. Thus, a large number of studies have investigated the risk factors for childhood asthma, with a meticulous search of modifiable factors that could aid in primary prevention.We present a current literature review from 2014-2017, as well as older classic publications, on the pathogenesis and the potential modifiable factors for primary prevention of asthma. No ideal preventive measure has yet been found. Rather, creating favorable prenatal and postnatal environments, minimal exposure to hostile environmental factors, prevention of infections in early life, allergic desensitization and nutritional modifications could possibly reduce asthma inception. In the era of personalized medicine, identifying individual risk factors and tailoring specific preventive measures is warranted.