CFTR variants are associated with chronic bronchitis in smokers

IntroductionLoss of function variants in both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF); however, there is evidence that reduction in CFTR function due to the presence of one deleterious variant can have clinical consequences. Here, we hypothesize that CFTR variants in individuals with a history of smoking are associated with COPD and related phenotypes.MethodsWhole genome sequencing was performed through the NHLBI TOPMed program in 8597 subjects from the COPDGene study, an observational study of current and former smokers. We extracted clinically annotated CFTR variants and performed single variant and variant-set testing for COPD and related phenotypes. Replication was performed in 2,118 subjects from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study.ResultsWe identified 301 coding variants within the CFTR gene boundary: 147 of these have been reported in individuals with CF, including 36 CF-causing variants. We found that CF causing variants were associated with chronic bronchitis in variant-set testing in COPDGene (one sided p-value=0.0025, OR=1.53) and in meta-analysis of COPDGene and ECLIPSE (one sided p-value=0.0060, OR=1.52). Single variant testing revealed that the F508del variant was associated with chronic bronchitis in COPDGene (one sided p-value=0.015, OR=1.47). In addition, we identified 32 subjects with two or more CFTR variants on separate alleles, and these subjects were enriched for COPD cases (p=0.010).ConclusionsCigarette smokers who carry one deleterious CFTR variant have higher rates of chronic bronchitis, while presence of two CFTR variants may be associated with COPD. These results indicate that genetically-mediated reduction in CFTR function contributes to COPD related phenotypes, in particular chronic bronchitis.

Chronic respiratory disease in adult outpatients in three African countries: a cross-sectional study

BACKGROUND: The greatest burden of chronic respiratory disease is in low- and middle-income countries, with recent population-based studies reporting substantial levels of obstructive and restrictive lung function.OBJECTIVE: To characterise the common chronic respiratory diseases encountered in hospital outpatient clinics in three African countries.METHODS This was a cross-sectional study of consecutive adult patients with chronic respiratory symptoms (>8 weeks) attending hospital outpatient departments in Ethiopia, Kenya and Sudan. Patients were assessed using a respiratory questionnaire, spirometry and chest radiography. The diagnoses of the reviewing clinicians were ascertained.RESULT: A total of 519 patients (209 Kenya, 170 Ethiopia, 140 Sudan) participated; the mean age was 45.2 years (SD 16.2); 53% were women, 83% had never smoked. Reviewing clinicians considered that 36% (95% CI 32–40) of patients had asthma, 25% (95% CI 21–29) had chronic bronchitis, 8% (95% CI 6–11) chronic obstructive pulmonary disease (COPD), 5% (95% CI 4–8) bronchiectasis and 4% (95% CI 3–6) post-TB lung disease. Spirometry consistent with COPD was present in 35% (95% CI 30–39). Restriction was evident in 38% (95% CI 33–43). There was evidence of sub-optimal diagnosis of asthma and COPD.CONCLUSION: In Ethiopia, Kenya and Sudan, asthma, COPD and chronic bronchitis account for the majority of diagnoses in non-TB patients with chronic respiratory symptoms. The suboptimal diagnosis of these conditions will require the widespread use of spirometry.

Evaluation of a novel CFTR potentiator in copd ferrets with acquired cftr dysfunction

Rationale.The majority of chronic obstructive pulmonary disease (COPD) patients have chronic bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in chronic bronchitis, but has not been proven in a controlled animal model with airway disease. Furthermore, the potential of CFTR as a therapeutic target has not been tested in vivo, given limitations to rodent models of COPD. Ferrets exhibit cystic fibrosis-related lung pathology when CFTR is absent and COPD with bronchitis following cigarette smoke exposure.Objectives.To evaluate CFTR dysfunction induced by smoking and test its pharmacologic reversal by a novel CFTR potentiator, GLPG2196, in a ferret model of COPD with chronic bronchitis.Methods.Ferrets were exposed for six months to cigarette smoke to induce COPD and chronic bronchitis and then treated with eneral GLPG2196 once daily for one month. Electrophysiologic measurements of ion transport and CFTR function, assessment of mucociliary function by one-micron optical coherence tomography imaging and particle tracking microrhelogy, microcomputed tomography imaging, histopathological analysis, and quantification of CFTR protein and mRNA expression were used to evaluate mechanistic and pathophysiological changes.Measurements and Main Results.Following cigarette smoke exposure, ferrets exhibited CFTR dysfunction, increased mucus viscosity, delayed mucociliary clearance, airway wall thickening, and airway epithelial hypertrophy. In COPD ferrets, GLPG2196 treatment reversed CFTR dysfunction, increased mucus transport by decreasing mucus viscosity, and reduced brochial wall thickening and airway epithelial hypertrophy.Conclusions.The pharmacologic reversal of acquired CFTR dysfunction is beneficial against pathologic features of chronic bronchitis in a COPD ferret model.

Decreased eosinophil counts and elevated lactate dehydrogenase predict severe COVID-19 in patients with underlying chronic airway diseases

BackgroundSeveral predictors of COVID-19 severity have been reported. However, chronic airway inflammation characterised by accumulated lymphocytes or eosinophils may affect the pathogenesis of COVID-19.MethodsIn this retrospective cohort study, we reviewed the medical records of all patients with laboratory-confirmed COVID-19 with chronic bronchitis, chronic obstructive pulmonary disease (COPD) and asthma admitted to the Sino-French New City Branch of Tongji Hospital, a large regional hospital in Wuhan, China, from 26 January to 3 April. The Tongji Hospital Ethics Committee approved this study.ResultsThere were 59 patients with chronic bronchitis, COPD and asthma. When compared with non-severe patients, severe patients were more likely to have decreased lymphocyte counts (0.6×10⁹/L vs 1.1×10⁹/L, p<0.001), eosinopaenia (<0.02×10⁹/L; 73% vs 24%, p<0.001), increased lactate dehydrogenase (LDH) (471.0 U/L vs 230.0 U/L, p<0.001) and elevated interleukin 6 level (47.4 pg/mL vs 5.7 pg/mL, p=0.002) on admission. Eosinopaenia and elevated LDH were significantly associated with disease severity in both univariate and multivariate regression models including the above variables. Moreover, eosinophil count and LDH level tended to return to normal range over time in both groups after treatment and severe patients recovered slower than non-severe patients, especially in eosinophil count.ConclusionsEosinopaenia and elevated LDH are potential predictors of disease severity in patients with COVID-19 with underlying chronic airway diseases. In addition, they could indicate disease progression and treatment effectiveness.

A COMPARATIVE CLINICAL STUDY TO EVALUATE THE EFFICACY OF LAVANGADI GUTIKA AND PIPPALYADI GUTIKA IN KAPHAJA KASA

Kasa is one of the Pranavaha Srothodusti vikara which hinders normal life. Kaphaja Kasa is a type of Kasa with Vata and Kapha as predominant doshas and present with Prabhuta, Ghana and Bahala kapha. Kaphaja Kasa can be best compared with Chronic Bronchitis. If left untreated it leads to various conditions like Swasa, Kshaya, Chardi, Svarasaadha etc. This signifies the importance of its early management. The present study was conducted on 40 diagnosed subjects of Kaphaja Kasa who were randomly allocated into 2 groups with 20 patients each. La- vangadi gutika was taken in Group A and Pippalyadi gutika in Group B. Medicines was given for 30 days and the data was collected from the subject at baseline, 16th day, 31st day and on 46th day (follow up). The result of the study showed that there was a statistically significant difference in the assessment parameters in both the groups from baseline. However no statistically significant difference was observed between the effect of Lavangadi guti- ka and Pippalyadi gutika in the management of Kaphaja Kasa suggesting that both interventions were having a significant effect on the condition.

The influence of smoking on the formation of occupational lung diseases in workers who come into contact with industrial aerosols

The formation of a healthy lifestyle is one of the most important tasks of disease prevention. Among the factors that negatively affect the health of the population, smoking is of great importance. The influence of smoking on the formation of occupational diseases in workers in harmful and (or) dangerous working conditions has not been sufficiently studied. Based on the knowledge of the pathogenesis of common diseases, it can be assumed with a high degree of probability that smoking can provoke the development of occupational pathology of the respiratory organs, malignant neoplasms, vascular pathology.The aim of the work was to study the clinical manifestations of chronic bronchitis, characterizing the state of the bronchopulmonary system, in smokers and non-smokers who had long-term contact with industrial dust, as well as to analyze the literature data on the impact of smoking on the development of occupational lung diseases in workers exposed to asbestos dust.Materials and methods of research. In the clinic “Research Institute of Occupational Medicine named after Academician N.F. Izmerov”, 55 workers were examined under the influence of industrial aerosols of fibrogenic action. The group of smokers consisted of 45 people: 25 people were coal miners, 20 people were foundry workers. The group of non-smokers consisted of 10 people: 6 coal miners and 4 foundry workers. The severity of the course of professional and non-professional chronic bronchitis in patients was assessed taking into account the clinical manifestations and frequency of exacerbations of the disease, as well as taking into account the severity of respiratory disorders and gas exchange disorders.Results and discussion. In the group of smoking patients, 93,3% had occupational chronic bronchitis, 6.7% had no such pathology. In the group of non-smoking patients with and without occupational chronic bronchitis, there were equally – 50,0%. In the group of smoking patients, 55,5 of the examined patients had respiratory insufficiency of the II degree; 15,5% were diagnosed with respiratory insufficiency of the III degree; cases without respiratory function impairment (DN0 art.) were only 8,8%. In the group of non-smoking patients, grade II DN was more than three times less frequent, amounting to 20,0%, while 40,0% had grade 0 DN and 40,0% had grade I DN; grade III DN was never diagnosed in this group of patients.Conclusion. Smoking, as an independent factor, can play a significant, and in some cases, obviously, a determining role in the development and progression of chronic bronchitis in people exposed to industrial aerosols.The health risks associated with tobacco should be taken into account as an integral part of the assessment of the risks of developing occupational diseases.

Description of Smoking Behavior in Adolescents During The Covid-Pandemic

The behaviors that young people exhibit in the COVID-19 era are the strong behaviors in which the four information ants interviewed have different behaviors in the experience, expectations, the number of cigarettes, and the type of cigarettes consumed. Smoking behavior is one form of behavior encountered in people's lives and can be found in various places such as in crowded places, streets, city buses, hospitals, schools, and so on. A smoking habit can cause damage to the lungs and airways that will cause diseases of the respiratory system, such as chronic bronchitis, emphysema, even lung cancer. Schools and People need to be involved in efforts to prevent and intervene in adolescent smoking behavior more intensively.

How to differentiate cardiac asthma from other asthmatic seizures and what treatment to use

Prof. I. Donath (Dio Arztrliche Praxis, No. 5, 1929. Medizinisches Seminar) notes cases of the possibility of an easy delimitation of cardiac or pulmonary asthma from other types of suffocation, and at the same time cases where it is very difficult to make such a delimitation, as, for example, in old people-emphysematics with chronic bronchitis and a weak heart who have shortness of breath as a result of both heart and lung disease. In these latter cases, anti-broncho-asthmatic agents (astmolysin, lysostmin, belladonna and iodine) are successfully used simultaneously with cardiac ones. For pure cardiac asthma, morphine and its derivatives remain the best remedy. Since in some cases it is impossible to establish the absence of a pulmonary component in the etiology of this asthma, and morphine is contraindicated in pure pulmonary asthma, morphine should always be given in combination with caffeine or cardiazole. In many cases, seizures are stopped by injections of pituitrin, pituisan or pituglandol in an amount of 0.5 to 1.0 cm3, as well as nitrites, theobromine, and teominal. Cases of cardiac asthma, leading to symptoms of heart failure and pulmonary edema, are subject to cardiodiuretic therapy, and the best and fastest way is intravenous administration of digipurate in combination with aminophylline or salirgan.