Development Of Airflow Obstruction Research Articles

Association of smoking cessation with airflow obstruction in workers with silicosis: A cohort study.

Studies in general population reported a positive association between tobacco smoking and airflow obstruction (AFO), a hallmark of chronic obstructive pulmonary disease (COPD). However, this attempt was less addressed in silica dust-exposed workers. This retrospective cohort study consisted of 4481 silicotic workers attending the Pneumoconiosis Clinic during 1981-2019. The lifelong work history and smoking habits of these workers were extracted from medical records. Spirometry was carried out at the diagnosis of silicosis (n = 4177) and reperformed after an average of 9.4 years of follow-up (n = 2648). AFO was defined as forced expiratory volume in one second (FEV1)/force vital capacity (FVC) less than lower limit of normal (LLN). The association of AFO with smoking status was determined using multivariate logistics regression, and the effect of smoking cessation on the development of AFO was evaluated Cox regression. Smoking was significantly associated with AFO (current smokers: OR = 1.92, 95% CI 1.51-2.44; former smokers: OR = 2.09, 95% CI 1.65-2.66). The risk of AFO significantly increased in the first 3 years of quitting smoking (OR = 1.23, 95% CI 1.02-1.47) but decreased afterwards with increasing years of cessation. Smoking cessation reduced the risk of developing AFO no matter before or after the confirmation of silicosis (pre-silicosis cessation: HR = 0.58, 95% CI 0.46-0.74; post-silicosis cessation: HR = 0.62, 95% CI 0.48-0.79). Smoking cessation significantly reduced the risk of AFO in the workers with silicosis, although the health benefit was not observed until 3 years of abstinence. These findings highlight the importance of early and long-term smoking cessation among silicotic or silica dust-exposed workers.

Preserved ratio impaired spirometry with or without restrictive spirometric abnormality

Preserved ratio impaired spirometry (PRISm) is defined by reduced FEV1 with a preserved FEV1/FVC ratio; some individuals with PRISm can also have restrictive ventilatory abnormality. The aim of this study was to clarify clinical features of restrictive and non-restrictive PRISm. In total, 11,246 participants (mean, 49.1 years; range, 35–65 years) from five healthcare centres were included in this study. We evaluated baseline characteristics of participants with restrictive PRISm (FEV1/FVC ≥ 0.7, FEV1 < 80% and FVC < 80%) and non-restrictive PRISm (FEV1/FVC ≥ 0.7, FEV1 < 80% and FVC ≥ 80%), and airflow obstruction (FEV1/FVC < 0.7). We examined the longitudinal risk of developing airflow obstruction by comparing spirometry results at baseline and 5 years post-baseline among 2141 participants. Multivariate analysis demonstrated that a history of asthma or smoking could constitute an independent risk factor for non-restrictive PRISm, and that non-restrictive PRISm was independently associated with the risk of developing airflow obstruction. In contrast, female sex, advanced age, and high BMI, but not history of asthma or smoking, were risk factors for restrictive PRISm. Restrictive PRISm was not associated with the development of airflow obstruction. In conclusion, our results indicate that PRISm can be categorized according to the presence or absence of restrictive abnormality. Non-restrictive PRISm, which does not meet the conventional criteria of obstructive and restrictive ventilatory abnormalities, may be a precursor of chronic obstructive pulmonary disease and merits increased monitoring.

Long-term exposure to air pollution and the development of airflow obstruction in the population-based Dutch Lifelines cohort

Long-term exposure to air pollution and the development of airflow obstruction in the population-based Dutch Lifelines cohort

407 - Microbiota Alteration Associates with Development of Airflow Obstruction after Allogeneic Hematopoietic Cell Transplantation

407 - Microbiota Alteration Associates with Development of Airflow Obstruction after Allogeneic Hematopoietic Cell Transplantation

Body mass index across adulthood and the development of airflow obstruction and emphysema.

Low body mass index (BMI) is associated with COPD, but temporal relationships between airflow obstruction (AO) development and emphysematous change are unclear. We investigated longitudinal changes in BMI, AO, and lung density throughout adulthood using data from the Framingham Offspring Cohort (FOC). BMI trajectories were modelled throughout adulthood in 4587 FOC participants from Exam 2 (mean age = 44), through Exam 9 (mean age = 71), in AO participants and non-AO participants (AO n = 1036), determined by spirometry, using fractional polynomial growth curves. This process was repeated for low lung density (LLD) and non LLD participants (LLD n = 225) determined by Computed Tomography. Spirometry decline was compared separately between tertiles of BMI in those aged <40years and associations between fat and lean mass (measured using Dual Energy X-ray Absorptiometry, DEXA) and development of AO and LLD were also assessed. Additional analyses were performed with adjustment for smoking volume. The BMI trajectory from 30years of age was visually lower in the AO group than both non-AO smokers (non-<AO-S) and non-AO non-smokers (non-AO-N). Similarly, BMI trajectories were visually lower in participants with LLD throughout adulthood compared to normal lung density smokers and non-smokers. Differences remained after adjustment for smoking volume. The lowest BMI tertile in ages <40years was associated with the steepest subsequent decline in FEV1/FVC ratio in both sexes. Mean BMI is lower throughout adulthood in AO and LLD participants. Lower BMI is associated with a steeper decline in the ratio of FEV1/FVC. These findings suggest body mass may precede and potentially have a role in the development of COPD lung pathophysiology.

Cohort profile: The Chikwawa lung health cohort; a population-based observational non-communicable respiratory disease study of adults in Malawi.

The aim of this article is to provide a detailed description of the Chikwawa lung health cohort which was established in rural Malawi to prospectively determine the prevalence and causes of lung disease amongst the general population of adults living in a low-income rural setting in Sub-Saharan Africa. A total of 1481 participants were randomly identified and recruited in 2014 for the baseline study. We collected data on demographic, socio-economic status, respiratory symptoms and potentially relevant exposures such as smoking, household fuels, environmental exposures, occupational history/exposures, dietary intake, healthcare utilization, cost (medication, outpatient visits and inpatient admissions) and productivity losses. Spirometry was performed to assess lung function. At baseline, 56.9% of the participants were female, mean age was 43.8 (SD:17.8) and mean body mass index (BMI) was 21.6 Kg/m2 (SD: 3.46). The cohort has reported the prevalence of chronic respiratory symptoms (13.6%, 95% confidence interval [CI], 11.9-15.4), spirometric obstruction (8.7%, 95% CI, 7.0-10.7), and spirometric restriction (34.8%, 95% CI, 31.7-38.0). Additionally, an annual decline in forced expiratory volume in one second [FEV1] of 30.9mL/year (95% CI: 21.6 to 40.1) and forced vital capacity [FVC] by 38.3 mL/year (95% CI: 28.5 to 48.1) has been reported. The ongoing phases of follow-up will determine the annual rate of decline in lung function as measured through spirometry and the development of airflow obstruction and restriction, and relate these to morbidity, mortality and economic cost of airflow obstruction and restriction. Population-based mathematical models will be developed driven by the empirical data from the cohort and national population data for Malawi to assess the effects of interventions and programmes to address the lung burden in Malawi. The present follow-up study started in 2019.

The Effect of Cigarette Smoking on Lung Function in Young Adults with Asthma.

Life-course persistent asthma and tobacco smoking are risk factors for irreversible airflow obstruction. It is often assumed that smoking and asthma have additive or multiplicative effects on the risk for airflow obstruction, but this has not been demonstrated in prospective studies of children with persistent asthma. To investigate the effects of smoking and asthma on the development of airflow obstruction in a population-based birth cohort followed to age 38 years. Reports of childhood asthma from ages 9, 11, and 13 and self-reports of adult asthma at ages 32 and 38 years were used to define childhood-onset persistent asthma (n = 91), late-onset asthma (n = 93), asthma in remission (n = 85), and nonasthmatic (n = 572) phenotypes. Cumulative tobacco smoking histories and spirometry were obtained at ages 18, 21, 26, 32, and 38 years. Analyses were by generalized estimating equations adjusting for childhood spirometry, body mass index, age, and sex. Smoking history and childhood-onset persistent asthma were both associated with lower FEV1/FVC ratios. Associations between smoking and FEV1/FVC ratios were different between asthma phenotypes (interaction P < 0.001). Smoking was associated with lower prebronchodilator and post-bronchodilator FEV1/FVC ratios among subjects without asthma and those with late-onset or remittent asthma, but smoking was not associated with lower FEV1/FVC ratios among those with childhood-onset persistent asthma. Childhood-onset persistent asthma is associated with airflow obstruction by mid-adult life, but this does not seem to be made worse by tobacco smoking. We found no evidence that smoking and childhood-persistent asthma have additive or multiplicative effects on airflow obstruction.

Pulmonary Physiology of Chronic Obstructive Pulmonary Disease, Cystic Fibrosis, and Alpha-1 Antitrypsin Deficiency.

Cystic fibrosis is predominantly an airway disease with marked bronchiectatic changes associated with inflammation, chronic colonization, and progressive airflow obstruction. The condition can be identified in childhood and monitored with detectable airway changes early in life while conventional spirometry remains in the normal range. Alpha-1 antitrypsin deficiency can also be detected early in life through blood spot and genetic testing and leads (in some) to the development of airflow obstruction and a predominant emphysema phenotype with bronchiectatic changes in about 30%. Early detection also allows the natural history of the pulmonary physiological changes to be determined. Chronic obstructive pulmonary disease is usually detected late in the disease process when significant damage has occurred. The condition consists of varying combinations of airway disease, bronchiectasis, colonization, and emphysema. Lessons learned from the physiological evolution of airway disease in cystic fibrosis and the emphysema of alpha-1 antitrypsin deficiency provide strategies to enable early detection of chronic obstructive pulmonary disease in general and its phenotypes.

Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the Development of Airflow Obstruction

Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the Development of Airflow Obstruction

Chronic airflow limitation in a rural Indian population: etiology and relationship to body mass index

PurposeRespiratory conditions remain a source of morbidity globally. As such, this study aimed to explore factors associated with the development of airflow obstruction (AFO) in a rural Indian setting and, using spirometry, study whether underweight is linked to AFO.MethodsPatients > 35 years old attending a rural clinic in West Bengal, India, took a structured questionnaire, had their body mass index (BMI) measured, and had spirometry performed by an ancillary health care worker.ResultsIn total, 416 patients completed the study; spirometry was acceptable for analysis of forced expiratory volume in 1 second in 286 cases (69%); 16% were noted to exhibit AFO. Factors associated with AFO were: increasing age (95% confidence interval (CI) 0.004–0.011; P = 0.005), smoking history (95% CI 0.07–0.174; P = 0.006), male gender (95% CI 0.19–0.47; P = 0.012), reduced BMI (95% CI 0.19–0.65; P = 0.02), and occupation (95% CI 0.12–0.84; P = 0.08). The mean BMI in males who currently smoked (n = 60; 19.29 kg/m2; standard deviation [SD] 3.46) was significantly lower than in male never smokers (n = 33; 21.15 kg/m2 SD 3.38; P < 0.001). AFO was observed in 27% of subjects with a BMI <18.5 kg/m2, falling to 13% with a BMI ≥18.5 kg/m2 (P = 0.013). AFO was observed in 11% of housewives, 22% of farm laborers, and 31% of cotton/jute workers (P = 0.035).ConclusionIn a rural Indian setting, AFO was related to advancing age, current or previous smoking, male gender, reduced BMI, and occupation. The data also suggest that being under-weight is linked with AFO and that a mechanistic relationship exists between low body weight, smoking tobacco, and development of AFO.

Azithromycin and bronchiolitis obliterans syndrome after lung transplantation: is prevention better than cure?

Although lung transplantation is now accepted as an established therapy for selected patients with end-stage lung disease, long-term survival after lung transplantation remains limited by the development of bronchiolitis obliterans syndrome (BOS) in >50% of recipients 1. BOS is the clinical manifestation of an inflammatory bronchiolitis associated with fibrotic remodelling of the small and medium-sized airways, and is characterised by progressive loss of allograft function with development of airflow obstruction 2, 3. Until recently, the development of BOS was associated with an irreversible and relentless decline in lung function, which either eventually stabilised at a very low level or, in many patients, progressed to end-stage respiratory failure, accounting for the commonest cause of death after the first post-transplant year. BOS has historically been attributed to the effects of ongoing alloimmune injury as both the frequency and severity of acute rejection episodes have been associated with increased risk 4. These observations lead to the paradigm that BOS is chronic rejection of the transplanted lung and, consequently, intensification of immunosuppression was used as an attempted therapy in many affected recipients. These approaches offered, at best, a slowing in the progression of the condition in some, but also contributed to infective complications that undoubtedly added to the overall mortality risk from BOS. Over the last decade, a number of clinical trials of more intensive immunosuppressive regimes from the time of transplant or after onset of BOS have failed to impact on the incidence of BOS or regaining of lost function 5, 6. More recently, however, it has been appreciated that nonalloimmune insults to the lung allograft, such as the lung injury of primary graft dysfunction, viral and bacterial infections, and aspiration injury, also increase the risk of developing BOS 7. This suggests that cross-talk between innate …

P121 Feasibility of performing valid spirometry in rural India: preliminary results from a population study assessing the prevalence of COPD

IntroductionSpirometry remains the cornerstone in the diagnosis of Chronic Obstructive Pulmonary Disease (COPD). Little is known regarding the determinants and prevalence of COPD in rural India. We undertook a population-based...

Asthma and COPD in Alpha-1 Antitrypsin Deficiency. Evidence for the Dutch Hypothesis

ABSTRACTThis review summarizes the current information on the relationship between severe alpha-1 antitrypsin deficiency (AATD), asthma and COPD. AATD is a genetic predisposition to the development of early COPD in susceptible individuals and reduction in known factors that enhance lung function loss is the paramount aim of management. Asthma is one controllable condition that leads to the accelerated decline in lung function. Current literature indicates that asthma signs and symptoms are common in those AATD with or without COPD and that bronchodilator response is a risk factor for FEV1 decline. Furthermore AATD itself predisposes to airway hyper responsiveness, an essential ingredient for reversible airflow obstruction. In the absence of well-characterized markers to distinguish COPD from asthma, clinical diagnosis leads to a delay in the recognition that asthma symptoms such as wheezing can be an early manifestation of COPD in AATD. In addition failure to appreciate asthma overlap in AATD may lead to inadequate suppression of airway inflammation leading to the development of airflow obstruction. The implications of this are discussed as are potential approaches and recommendations for treatment.

Differential distribution of inflammatory cells in large and small airways in smokers

Background: Smoking induces structural changes in the airways, and is considered a major factor in the development of airflow obstruction in chronic obstructive pulmonary disease. However, differences in inflammatory cell...

Genetic variation in bactericidal/permeability-increasing protein influences the risk of developing rapid airflow decline after hematopoietic cell transplantation

Innate immunity is involved in the biology of graft versus host disease and common airway diseases. We screened 15 genes in this pathway using a linkage disequilibrium-based approach to identify potential candidate genes that may be involved in the development of airflow obstruction after hematopoietic cell transplantation. Sixty-nine single-nucleotide polymorphisms were selected for assessment in a discovery cohort (n = 363). Significant associations were validated in a validation cohort (n = 209). Expression of the candidate gene was demonstrated by detecting gene transcript and protein in malignant and normal small airway epithelial cells. In the discovery cohort, 133 patients developed significant airflow decline. Four patient and donor bactericidal/permeability-increasing (BPI) haplotypes were associated with a 2-fold to 3-fold increased risk of developing significant airflow decline (P values, .004-.038). This association was confirmed in the validation cohort, which had 66 patients with significant airflow decline, with 9 significant haplotypes (P values, .013-.043). BPI gene transcript and protein were detected in airway epithelial cells. These results suggest mutations in the BPI gene significantly influence the risk of developing rapid airflow decline after hematopoietic cell transplantation and may represent a novel therapeutic target for this form of airway disease.

Implications of early airflow decline after myeloablative allogeneic stem cell transplantation.

The clinical significance of early airflow decline after myeloablative allogeneic hematopoietic SCT is uncertain. We performed a retrospective cohort analysis to determine if airflow decline by day 100 is associated with later development of transplant-related airflow obstruction (AFO) and increased mortality risk. Overall, 750 (40%) patients had airflow decline by day 100. Development of airflow decline by day 100 was associated with an increased risk for AFO at 1 year (relative risk 2.6, 95% confidence interval 2.1-3.1) but not with an increase in mortality risk (hazard ratio (HR) 0.86, P=0.05). However, patients with the fastest rate of decline between day 100 and 1 year (12.5% per year +/-24) had the highest mortality risk (HR 3.2, P<0.001). In conclusion, airflow measurements made on day 100 do not predict the rate of airflow decline between day 100 and 1 year, and therefore are not useful as a single measurement for determining mortality risk associated with development of AFO. Closer monitoring of the rate of airflow decline during the first year may facilitate the timely detection and treatment of early airflow decline and prevent the development of fixed AFO and increased mortality risk after hematopoietic stem cell transplant.

Non-endocrine late complications of bone marrow transplantation in childhood: part I.

Non-endocrine late complications of bone marrow transplantation in childhood: part I.

Role of Endogenous Nitric Oxide in Airflow Obstruction in Smokers

The aim of this study was to examine the relationship between endogenous nitric oxide (NO) level and airflow obstruction in smokers using single-breath measurement of exhaled NO with the sequential breath-holding method. A university hospital. Nine nonsmoking and ten smoking healthy volunteers. NO in exhaled air was measured using a chemiluminescence analyzer. Pulmonary function tests were performed using an autospirometer. The level of exhaled NO was higher in nonsmokers than in smokers, and the difference became larger as the breath-holding time increased. To evaluate the correlation between endogenous NO level and the degree of airflow obstruction in smokers, we used a new parameter, the NO concentration difference (delta NO). Our findings indicate that reduced level of NO in exhaled air is an indicator of decreased NO synthesis within the respiratory system and is associated with the development of airflow obstruction in smokers (r = 0.678; p < 0.01). delta NO is a good indicator of the synthesis of endogenous NO within the respiratory system, and it appears likely that the reduced synthesis of NO may be a contributing factor to airflow obstruction in smokers.

The relationship between wheezing and lung mechanics during methacholine-induced bronchoconstriction in asthmatic subjects.

Wheeze is a classic sign of airflow obstruction but relatively little is known of its mechanism of production or its relationship to the development of airflow obstruction. We studied eight asthmatic subjects age (mean +/- 5D) 42 +/- 5 yr, FEV1 2.46 +/- 0.36 L during an extended, symptom-limited methacholine challenge test. Breath sounds were detected by a microphone over the right upper anterior chest. Spectral analysis was by a fast Fourier transform algorithm. Mean FEV1 fell by 51 +/- 14% to 1.28 +/- 0.61 L during the challenge and airways resistance increased by 119 +/- 50%. There were no consistent changes in breathing pattern or tidal volume during the challenge. Wheeze occurred late in the challenge at the highest concentration of methacholine administered and only after expiratory tidal flow limitation had been reached. Five subjects developed wheeze on tidal breathing, the remaining three only wheezed on deep breathing. Wheezing sounds were reproducible between breaths, coefficient of variation of starting sound frequency was 4.2% and ending frequency 12%. Mean frequency of expiratory wheezes was 669 +/- 100 Hz and inspiratory wheezes 710 +/- 76 Hz. Expiratory wheeze fell in pitch during a breath (mean fall in sound frequency 187 +/- 43 Hz) but inspiratory wheezes were more variable. Expiratory wheezes occurred late in the respiratory cycle at a mean of 58% of the maximal tidal expiratory flow, whereas inspiratory wheezes occurred around maximal tidal inspiratory flows, suggesting that the mechanisms of production of inspiratory and expiratory wheezes may be different. In this model, the presence of wheeze during tidal breathing was a sign of severe airflow limitation.

Respiratory effects of coal dust exposure: clinical effects and diagnosis.

During the past two decades, growing evidence has been reported on the role of respirable inorganic dust in the development of airflow obstruction, impaired diffusion capacity, chronic bronchitis, and emphysema, irrespective of the extent of possible pneumoconiotic abnormalities. These nonpneumoconiotic effects associated with dust exposure in miners and the relationship between dust exposure and mortality are reviewed. When pneumoconiotic changes can be visualized by different radiologic techniques, including computed tomography (CT) and high-resolution CT, assessment of the respiratory impairment in coal workers at present requires evaluation of the ventilatory and gas exchange capacity.