Mean Decline In FEV1 Research Articles

Accelerated decline in lung function is associated with cardiac structure and function and independently predicts incident heart failure

Abstract Background The association between impaired lung function and cardiovascular disease is well known. However, it is not fully understood how a decline in lung function affects the development of cardiovascular disease including heart failure (HF). Purpose We aimed to investigate the association between declining lung function and changes in cardiac structure and function. Furthermore, we investigated the association between a decline in lung function and the risk of HF. Methods The study included 2,995 participants from a general population study. All participants had two examinations with spirometry performed 10 years apart. Participants were free of valvular heart disease and HF. A subsample (n=1,164) was also examined with echocardiography at both timepoints. The decline in the forced expiratory volume in one second (dFEV1) from the first visit to the second visit, was calculated. The change in cardiac structure and function between the two visits, was calculated as the decline in left ventricular ejection fraction (dLVEF), global longitudinal strain (dGLS), left ventricular mass index (dLVMi) and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (dE/e’). Linear regression models were adjusted for the baseline FEV1 and echocardiographic value to account for regression to the mean. Outcome was incident HF. Results The entire sample consisted of 57% women, and the mean age was 62 ± 14 years. A total of 59% had hypertension, 8% had ischemic heart disease (IHD), 6% had diabetes, and 18% were active smokers. Mean FEV1 at baseline was 2.8 ± 0.95 liters (95 ± 19% as percentage of the predicted value). The mean decline in FEV1 between visits (median 10.8 years, IQR: 10.3-11.2) was 309 ± 362 mL. In the subsample examined with echocardiography, decreasing dLVEF was significantly associated with decreasing dFEV1 (p=0.030) in multivariable linear regression analysis, whereas dGLS, dLVMi, and dE/e’ were not. In the total study sample, 105 participants developed incident heart failure following the second visit during a median follow-up of 5.4 years (IQR: 4.5-6.3). Participants in the lowest quartile of dFEV1 (no change or increase) had an incidence rate of 2.48 per 1,000 person years (95%CI 1.33-4.60) versus participants in the highest quartile of dFEV1 (largest decline) with an incidence rate of 13.9 per 1,000 person years (95%CI 10.6-18.3), p<0.001. In multivariable Cox regression analysis, dFEV1 was an independent predictor of HF with a hazard ratio of 3.37 per 1 liter decline (95%CI 1.53-7.43, p=0.003). Conclusion We found a strong association between a decline in FEV1 and a decline in LVEF over a decade. Decreasing FEV1 was independently associated with incident HF. The incidence was highest for those with the largest decline in FEV1.A) Linear association B) Hist. of dLVEFA) Incidence rate B) Cumulative inc.

Annual FEV1 Loss in Patients with Noncystic Fibrosis Bronchiectasis and Affecting Factors.

Bronchiectasis is a chronic respiratory disease characterized by sputum production, cough, and several bronchial infections. Lung function is an important parameter to evaluate and study in patients with bronchiectasis. This study aimed to evaluate the annual changes in forced expiratory volume in one second (FEV1) and related factors in patients with with noncystic fibrosis bronchiectasis. A total of 529 patients who were diagnosed as having bronchiectasis using computed tomography and followed at the bronchiectasis unit of the Cerrahpasa Medical Faculty at Istanbul University between 1996 and 2018 were included in this retrospective study. A total of 153 patients were included in the study. The mean age of the patients was 58.6 ± 16.8 years and 61% (n = 93) were female. The annual change of FEV1 and forced vital capacity was -39 ± 82 (minimum: -585, maximum: 355, median: -26) mL and - 44 ± 91 (minimum: -517, maximum: 303, median: -31) mL, respectively. There was no correlation in FEV1 decline between those with and without Pseudomonas colonization (P = 0.65). No correlation was found between the etiologic factors and the decline of FEV1. A correlation existed only between the first FEV1 and the decline of FEV1 (for the first FEV1%, P = 0.038 [R = -0.17]; for the first FEV1 [mL] P = 0.026 [R = -0.18]). An annual mean FEV1 loss of 39 mL was found in adult patients with noncystic fibrosis bronchiectasis. The annual mean FEV1 decline was found to be associated with the baseline FEV1 value. Physicians should exercise caution in this regard in patients with bronchiectasis with low FEV1 values.

Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database.

BackgroundPatients with ZZ (Glu342Lys) α-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with α-1-antitrypsin (AAT) in randomised controlled trials over 2–3 years failed to show a significant reduction of the annual decline of forced expiratory volume in 1 s (FEV1).MethodsTo compare the trajectory of FEV1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV1 values entered in the Alpha-1 International Registry (AIR) of ZZ-AATD patients from five different European countries (Germany, UK, Spain, Italy and the Netherlands) was performed. The post-bronchodilator FEV1 % predicted values for baseline and follow-up over time from patients were analysed using linear mixed effects models.ResultsData of 374 patients were analysed: 246 untreated and 128 treated with intravenous AAT augmentation therapy. The mean±sd follow-up duration of the untreated group was 8.60±3.34 years and 8.59±2.62 years for the treated group. The mixed effects model analysis showed a mean FEV1 decline of −0.931% predicted per year (95% CI −1.144 to −0.718) in the untreated group and a decline of −1.016% predicted per year (95% CI −1.319 to −0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups (p=0.71).ConclusionIn our study population, we could not detect a significant difference in the annual decline of FEV1 by AAT augmentation treatment over a mean period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.

Relationship between metabolic syndrome and pulmonary function in workers with respiratory dust exposure in Iran

Aimswe designed a study to investigate the relationship between metabolic syndrome (MetS) and lung function in workers with dust exposure based on five years of longitudinal study data. MethodsIn this historical cohort study that conducted in iron ore mine, non-smoker male workers who exposed to dust, were enrolled. MetS was determined according to the National Cholesterol Education Program Adult Treatment Panel III. New spirometry parameters and spirometry from 5 years ago, were compared. ResultsIn this study 192 workers were identified without MetS and 77 with MetS. The mean of all lung parameters was lower in subjects with MetS, but it was not statistically significant. The median decline in FEV1 and FVC in 5 years was greater in subjects with MetS but were only significant for a decline in FEV1 (P-Value = 0.04). Linear regression analysis showed a significant relationship between a decline in FEV1 and waist circumference (P-Value = 0.001) when adjusted for age, BMI, physical activity level. ConclusionIn this study, a significant association between mean decline in FEV1 in 5 years and MetS in dust-exposed workers was demonstrated. Decline in FEV1 in 5 years was significantly associated with a Waist circumference as one of the components of MetS.

Vitamin D deficiency and lung function decline in healthy individuals: A large longitudinal observation study

AimA reliable evidence from a comprehensive large-scale study supporting associations between serum vitamin D (25-hydroxyvitamin D) level (SVDL) and lung function decline (LFD) in healthy individuals has been unavailable. Using a well-established health screening database, we assessed the associations between SVDL and LFDs, measured as the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. MethodsSerial SVDL and lung function data were analyzed using linear mixed models, which were performed in smokers and non-smokers, separately. Vitamin D-deficient individuals (VDDs) were defined when their SVDLs were consistently lower than 20 ng/mL at all measurements. ResultsA total of 1371 individuals were analyzed. The mean FEV1 decline rates of VDDs and vitamin D-normal individuals (VDNs) in smokers were −33.35 mL/year (95% CI: 39.44 to −27.26 mL/year) and −15.61 mL/year (95% CI: 27.29 to −4.21 mL/year) respectively, over a mean of 6.29 years of observation with statistical significance (P < 0.001). However, there was no significant differences observed between decline rates of FEV1 in non-smokers. Similarly, FVC decline rates of VDDs were significantly greater than those of VDNs only in smokers (P < 0.001). However, FEV1/FVC ratio decline rates showed no significant difference between VDDs and VDNs regardless of their smoking status. ConclusionsConsistently low SVDLs predicted more rapid FEV1 and FVC declines in smokers. However, FEV1/FVC decline rate was not associated with SVDL. SVDL may be used to identify healthy smoking individuals at high risk for accelerated LFD.

A prognostic model of excessive lung function decline among Québec apprentices: a cohort exposed to occupational sensitizing agents

BACKGROUND Forced expiratory volume in 1 second (FEV1) decline as a predictor of lung-related health problems is widely observed, but not fully investigated. This study aimed to develop models to predict FEV1 decline among apprentices exposed to sensitizing agents. METHODS Of 692 apprentices recruited and followed in 3.6–17.3 years, 292 were exposed to low-molecular weight agents. The analysis was restricted to 357 apprentices with complete lung function assessment at the end of their training with a minimum of 5-year follow-up. According to the American Thoracic Society guideline, a mean FEV₁ decline &gt;60 ml/year was defined as “accelerated.” Descriptive statistics and Cox regression analysis were utilized to determine its predictors. To develop the prognostic models, we used a logistic regression analysis adjusted for the follow-up duration. The accuracy of the models was quantified using calibration and discrimination measures. RESULTS Of 357 subjects, 62 (17.4%) had an excessive FEV1 decline post-apprenticeship. The questionnaire model (model 1), which included male sex, wheezing, and exposure to isocyanate or animal allergens during the apprenticeship, showed a reasonable discriminative ability (area under the receiver operating characteristics curve [AUC] of 0.67, 95% CI = 0.59–0.75). Adding the percent-predicted FEV₁ value at the end of apprenticeship significantly increased the discriminative ability of the model (model 4) (AUC = 0.762, 95% CI = 0.694–0.829) with a good calibration and reasonable internal validity. CONCLUSIONS We developed a model for accelerated lung function decline with a good accuracy and internal validity. However, external validation of the model is necessary.

Updated prevalence, predictors and treatment outcomes for bronchiolitis obliterans syndrome after allogeneic stem cell transplantation

IntroductionBronchiolitis obliterans syndrome (BOS) after allogeneic haemopoietic stem cell transplant (HSCT) is an under-recognised and difficult to treat disease. This occurs in the context of limited clinical research and inconsistent diagnostic criteria. MethodRetrospective data was collected on 275 patients who underwent allogeneic HSCT at an Australian tertiary hospital between 2007 and 2017. The prevalence of BOS, defined by 2014 National Institute of Health criteria, as well as predictors for BOS and mortality were determined. Treatment outcomes, using serial spirometry, were compared between patients who received early versus late immunosuppression for BOS. ResultsThe prevalence of BOS was 9.1%. Myeloablative conditioning (OR: 2.7, 95%CI: 1.13–6.50, p = 0.03) and extra-pulmonary chronic graft-versus-host disease (OR 2.62, 95% CI: 1.04–6.60, p = 0.04) were associated with BOS. There was reduced median survival in the BOS group compared with the non-BOS group, but this was not statistically significant (4.1years (IQR: 2.8, 6.8) versus 4.6years (IQR: 2.4, 7.8), respectively, p = 0.33). The vast majority (87.5%) of BOS patients failed to attain improvement in FEV1 at 12 months, regardless of treatment strategy. Patients who underwent a late immunosuppression strategy had worse mean FEV1 decline compared to those who received early immunosuppression (−36.3% versus −1.6%, respectively, p = 0.03). ConclusionBOS is a common and progressive disease following HSCT and is largely refractory to current treatment strategies. Compared to late immunosuppression, early augmentation of immunosuppression may slow lung function deterioration in the short term. However, further research is urgently needed to identify effective prevention and treatment strategies for BOS.

Association of Dysanapsis With Chronic Obstructive Pulmonary Disease Among Older Adults

Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), yet much of COPD risk remains unexplained. To determine whether dysanapsis, a mismatch of airway tree caliber to lung size, assessed by computed tomography (CT), is associated with incident COPD among older adults and lung function decline in COPD. A retrospective cohort study of 2 community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which involved 2531 participants (6 US sites, 2010-2018) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved 1272 participants (9 Canadian sites, 2010-2018), and a case-control study of COPD: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which involved 2726 participants (12 US sites, 2011-2016). Dysanapsis was quantified on CT as the geometric mean of airway lumen diameters measured at 19 standard anatomic locations divided by the cube root of lung volume (airway to lung ratio). Primary outcome was COPD defined by postbronchodilator ratio of forced expired volume in the first second to vital capacity (FEV1:FVC) less than 0.70 with respiratory symptoms. Secondary outcome was longitudinal lung function. All analyses were adjusted for demographics and standard COPD risk factors (primary and secondhand tobacco smoke exposures, occupational and environmental pollutants, and asthma). In the MESA Lung sample (mean [SD] age, 69 years [9 years]; 1334 women [52.7%]), 237 of 2531 participants (9.4%) had prevalent COPD, the mean (SD) airway to lung ratio was 0.033 (0.004), and the mean (SD) FEV1 decline was -33 mL/y (31 mL/y). Of 2294 MESA Lung participants without prevalent COPD, 98 (4.3%) had incident COPD at a median of 6.2 years. Compared with participants in the highest quartile of airway to lung ratio, those in the lowest had a significantly higher COPD incidence (9.8 vs 1.2 cases per 1000 person-years; rate ratio [RR], 8.12; 95% CI, 3.81 to 17.27; rate difference, 8.6 cases per 1000 person-years; 95% CI, 7.1 to 9.2; P < .001) but no significant difference in FEV1 decline (-31 vs -33 mL/y; difference, 2 mL/y; 95% CI, -2 to 5; P = .30). Among CanCOLD participants (mean [SD] age, 67 years [10 years]; 564 women [44.3%]), 113 of 752 (15.0%) had incident COPD at a median of 3.1 years and the mean (SD) FEV1 decline was -36 mL/y (75 mL/y). The COPD incidence in the lowest airway to lung quartile was significantly higher than in the highest quartile (80.6 vs 24.2 cases per 1000 person-years; RR, 3.33; 95% CI, 1.89 to 5.85; rate difference, 56.4 cases per 1000 person-years; 95% CI, 38.0 to 66.8; P<.001), but the FEV1 decline did not differ significantly (-34 vs -36 mL/y; difference, 1 mL/y; 95% CI, -15 to 16; P=.97). Among 1206 SPIROMICS participants (mean [SD] age, 65 years [8 years]; 542 women [44.9%]) with COPD who were followed up for a median 2.1 years, those in the lowest airway to lung ratio quartile had a mean FEV1 decline of -37 mL/y (15 mL/y), which did not differ significantly from the decline in MESA Lung participants (P = .98), whereas those in highest quartile had significantly faster decline than participants in MESA Lung (-55 mL/y [16 mL/y ]; difference, -17 mL/y; 95% CI, -32 to -3; P = .004). Among older adults, dysanapsis was significantly associated with COPD, with lower airway tree caliber relative to lung size associated with greater COPD risk. Dysanapsis appears to be a risk factor associated with COPD.

Longitudinal decline in lung function: a community-based cohort study in Korea

Progressive decline in lung function is the hallmark of chronic obstructive pulmonary disease (COPD). We aimed to assess the rate of decline in forced expiratory volume in 1 second (FEV1) in patients from a community cohort database in Korea. 5,865 subjects aged 40–69 years from the Ansung-Ansan cohort database I–III (2001–2006) were included in this study. We assessed the annual rate of decline in FEV1 over time in relation to smoking status, patient sex, and presence or absence of pre-bronchodilator airflow limitation using a generalized additive mixed model. The mean follow-up duration was 3.8 years. The annual mean decline in FEV1 in the entire cohort was significantly more rapid for men than women (31.3 mL vs 27.0 mL, P = 0.003). Among men without pre-bronchodilator airflow limitation, annual mean declines in FEV1 were 31.5, 35.5, and 40.1 mL for never smokers, former smokers (P = 0.09 vs. never smokers), and current smokers (P < 0.001 vs. never smokers), respectively; and 23.4, 19.7, and 33.9 mL, respectively, for men with pre-bronchodilator airflow limitation. Thus, among Korean males, smoking accelerates lung function decline over time whereas smoking cessation slows the rate of FEV1 decline regardless of pre-bronchodilator airflow limitation. This underscores the importance of smoking cessation in Koreans.

Albuminuria, Lung Function Decline, and Risk of Incident Chronic Obstructive Pulmonary Disease. The NHLBI Pooled Cohorts Study.

Chronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD. To test whether albuminuria was associated with lung function decline and incident CLRDs. Six U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications. Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV1 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV1 decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV1/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P < 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease. Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population-based sample.

Long-term evolution of lung function in individuals with alpha-1 antitrypsin deficiency from the Spanish registry (REDAAT).

BackgroundThe clinical course of alpha-1 antitrypsin deficiency (AATD) is very heterogeneous. It is estimated that 60% of individuals with severe AATD (Pi*ZZ) develop emphysema. The main objective of this study was to describe the outcomes of long-term lung function in individuals with AATD-associated emphysema after at least 8 years of follow-up.Materials and methodsWe performed a retrospective analysis of longitudinal follow-up data of AATD PiZZ patients from the Spanish registry (AATD Spanish Registry [REDAAT]). The main follow-up outcome was the annual rate of decline in forced expiratory volume in 1 second (FEV1) calculated using the FEV1 values at baseline and in the last post-bronchodilator spirometry available.ResultsOne hundred and twenty-two AATD PiZZ patients were analyzed. The median follow-up was 11 years (interquartile range =9–14). The mean FEV1 decline was 28 mL/year (SD=54), with a median of 33 mL/year. Tobacco consumption (β=19.8, p<0.001), previous pneumonia (β=27.8, p=0.026) and higher baseline FEV1% (β=0.798, p=0.016) were independently related to a faster FEV1 decline.ConclusionIn this large cohort with a long follow-up, we observed a very variable decline of FEV1. However, the mean FEV1 decline was similar to that observed in large cohorts of smoking-related COPD. Tobacco consumption, previous pneumonia and better lung function at baseline were related to a faster decline in FEV1. These results highlight the importance of early diagnosis and effective treatment.

Computed Tomography Measure of Lung at Risk and Lung Function Decline in Chronic Obstructive Pulmonary Disease.

The rate of decline of lung function is greater than age-related change in a substantial proportion of patients with chronic obstructive pulmonary disease, even after smoking cessation. Regions of the lung adjacent to emphysematous areas are subject to abnormal stretch during respiration, and this biomechanical stress likely influences emphysema initiation and progression. To assess whether quantifying this penumbra of lung at risk would predict FEV1 decline. We analyzed paired inspiratory-expiratory computed tomography images at baseline of 680 subjects participating in a large multicenter study (COPDGene) over approximately 5 years. By matching inspiratory and expiratory images voxel by voxel using image registration, we calculated the Jacobian determinant, a measure of local lung expansion and contraction with respiration. We measured the distance between each normal voxel to the nearest emphysematous voxel, and quantified the percentage of normal voxels within each millimeter distance from emphysematous voxels as mechanically affected lung (MAL). Multivariable regression analyses were performed to assess the relationship between the Jacobian determinant, MAL, and FEV1 decline. The mean (SD) rate of decline in FEV1 was 39.0 (58.6) ml/yr. There was a progressive decrease in the mean Jacobian determinant of both emphysematous and normal voxels with increasing disease stage (P < 0.001). On multivariable analyses, the mean Jacobian determinant of normal voxels within 2 mm of emphysematous voxels (MAL2) was significantly associated with FEV1 decline. In mild-moderate disease, for participants at or above the median MAL2 (threshold, 36.9%), the mean decline in FEV1 was 56.4 (68.0) ml/yr versus 43.2 (59.9) ml/yr for those below the median (P = 0.044). Areas of normal-appearing lung are mechanically influenced by emphysematous areas and this lung at risk is associated with lung function decline. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Lung function and respiratory symptoms among female hairdressers in Palestine: a 5-year prospective study

BackgroundHairdressers are at risk of respiratory health problems due to exposure to chemicals in the workplace. We aimed to examine possible changes in self-reported respiratory symptoms and lung function over 5 years. Also, we examined the associations between occupational factors and lung function changes between baseline and follow-up. MethodsA cohort of 170 female hairdressers in Hebron answered a questionnaire and did a lung function test in 2008. A follow-up study was conducted on the same cohort in 2013. Changes in respiratory symptoms and lung function over the period were measured using generalised and linear mixed models. The lung function test was done using a PC spirometer and a disposable mouthpiece filter and nose clip. Participants were given instructions on the forced maximal expiratory manoeuvres. Respiratory symptoms that were assessed with the questionnaire included chest tightness, shortness of breath, wheezing, cough, and phlegm during the past 12 months. Furthermore, we asked questions on doctor-diagnosed asthma. Differences between current and former hairdressers in respiratory symptoms and lung function at follow-up were measured using mixed models. Written informed consent was obtained from all participants. Findings161 individuals participated in the follow-up study. 28 (16%) of the participants had left their profession. Current hairdressers reported significantly greater changes in chest tightness (prevalence difference [PD] 0·037, 95% CI 0·005 to 0·069) and shortness of breath (0·038, 0·001 to 0·076) between baseline and 2013, compared with former hairdressers Former hairdressers reported fewer symptoms at follow-up than did current hairdressers (PD 0·071, 95% CI –0·0167 to 0·024 for wheezing; 0·071, CI –0·167 to 0·023 for shortness of breath). At follow-up current hairdressers showed a significant decrease in forced expiratory volume in 1 s (FEV1) of 31 mL per year (95% CI 25 to 36). Hairdressers who had been working for 4 years or longer at baseline showed a stronger annual mean decline in FEV1 than those who had worked for less than 4 years (difference 13 mL, 95% CI 1 to 25). InterpretationCurrent hairdressers developed more respiratory symptoms and had a larger lung function decline than former hairdressers. Working for more years was associated with increased lung function decline. These findings suggest that workplace-related factors, including chemical exposures, might have a negative effect on the respiratory health of hairdressers. Thus, there might be a need to monitor exposures and eventually improve the workplace conditions. FundingNUFU “Building Competence in Epidemiology in Palestine” Pro 50-2002 and supportive measures 2008–2009.

Menopause Is Associated with Accelerated Lung Function Decline.

Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. To study whether lung function decline, assessed by FVC and FEV1, is accelerated in women who undergo menopause. The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

Six Minute Walk Test: A Tool for Predicting Mortality in Chronic Pulmonary Diseases.

Six Minute Walk Test (6MWT) is a simple test used to measure exercise capacity in Chronic Pulmonary Diseases (CPDs). Decreased exercise capacity significantly affects the quality of life. The 6MWT is a known tool to measure exercise capacity and quality of life in CPD. However, the role of change in follow up Six Minute Walk Distance (6MWD) in assessing mortality and its correlation with known prognostic factors haven't been tested to the best of our knowledge. To study the correlation of change in 6MWD with change in spirometry and to study the role of 6MWD in predicting mortality in CPD. Prospective cohort study. A total of 139 CPD patients were grouped into obstructive, restrictive and post Tuberculosis (TB) sequelae. Optimized treatment was given and they were followed up regularly. Spirometry and 6MWT was done at the beginning and after one year. Mean decline in FEV1, FVC was correlated with mean decline in 6MWD. With STATA 13.1 correlation between 6MWT and spirometric values were done using Wilcoxon signed rank test. Predictors of mortality were studied using multivariate analysis. Overall mean decline in 6MWD was 16.07 m/year. There was no correlation between mean change in 6MWD and change in FEV1, FVC, and FEV1/FVC. On multivariate analysis, 6MWD was the better predictor of mortality than FEV1 (p<0.001), FVC (p<0.001). At cut off value of 240 meters, sensitivity and specificity of 6MWT in predicting mortality was 71.05% and 81.94% respectively. The 6MWD changes independently and has no correlation with change in spirometry, it is an independent predictor of mortality in CPD.

Constrictive Bronchiolitis in Cystic Fibrosis Adolescents with Refractory Pulmonary Decline.

Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in cystic fibrosis (CF). To investigate the histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood, we reviewed clinically-indicated lung biopsy specimens obtained during a period of persistent decline. To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in adolescents with CF refractory to conventional therapy. Six adolescents with CF (mean age, 16.2 y; mean FEV1, 52% predicted at biopsy) with significant pulmonary deterioration over 12-24 months (mean FEV1 decline of 14% predicted/year) despite aggressive intervention underwent computed tomography imaging and ultimately lung biopsy to aid clinical management. In addition to routine clinical evaluation, histopathologic investigation included staining for transforming growth factor-β (TGF-β, a genetic modifier of CF lung disease), collagen deposition (a marker of fibrosis), elastin (to evaluate for bronchiectasis), and α-smooth muscle actin (to identify myofibroblasts). All computed tomography scans demonstrated a mix of bronchiectasis and hyperinflation that was variable across lung regions and within patients. Lung biopsy revealed significant peribronchiolar remodeling, particularly in patients with more advanced disease, with near complete obliteration of the peribronchiolar lumen (constrictive bronchiolitis). Myofibroblast differentiation (a TGF-β-dependent process) was prominent in specimens with significant airway remodeling. Constrictive bronchiolitis is widely present in the lung tissue of adolescents with CF with advanced disease and may contribute to impaired lung function that is refractory to conventional therapy (antibiotics, antiinflammatories, and mucolytics). TGF-β-dependent myofibroblast differentiation is prominent in areas of active fibrogenesis and may foster small airway remodeling in CF lung disease.

Physical activity and lung function decline in adults with asthma: The HUNT Study.

People with asthma may seek advice about physical activity. However, the benefits of leisure time physical activity on lung function are unclear. We investigated the association between leisure time physical activity and lung function decline in adults with asthma. In a population-based cohort study in Norway, we used multiple linear regressions to estimate the annual mean decline in lung function (and 95% CI) in 1329 people with asthma over a mean follow-up of 11.6 years. The durations of light and hard physical activity per week in the last year were collected by questionnaire. Inactive participants did not report any light or hard activity, while active participants reported light or hard activity. The mean decline in forced expiratory volume in 1 s (FEV1 ) was 37 mL/year among inactive participants and 32 mL/year in active participants (difference: -5 mL/year (95% CI: -13 to 3)). The mean decline in forced vital capacity (FVC) was 33 mL/year among inactive participants and 31 mL/year in active participants (difference: -2 mL/year (95% CI: -11 to 7)). The mean decline in FEV1 /FVC ratio was 0.36%/year among inactive participants and 0.22%/year in active participants (difference: -0.14%/year (95% CI: -0.27 to -0.01)). The mean decline in peak expiratory flow (PEF) was 14 mL/year among the inactive participants and 10 mL/year in active participants (difference: -4 mL/year (95% CI: -9 to 1)). We observed slightly less decline in lung function in physically active than inactive participants with asthma, particularly for FEV1 , FEV1 /FVC ratio and PEF.

Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease

BackgroundChronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms.MethodsWe stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end.ResultsAmong 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV1 before 40 years of age and had a rapid decline in FEV1 thereafter, with a mean (±SD) decline of 53±21 ml per year. The remaining half had had a low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27±18 ml per year (P<0.001), despite similar smoking exposure.ConclusionsOur study suggests that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV1 is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.)

Spanish Registry of Patients With Alpha-1 Antitrypsin Deficiency; Comparison of the Characteristics of PISZ and PIZZ Individuals

Alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of pulmonary emphysema and liver disease. The growing interest in this deficiency in Spain led to the development of the Spanish Registry of Patients with Alpha-1 Antitrypsin Deficiency (REDAAT) in 1993. At present, the REDAAT is a network of more than 350 health care professionals and the database includes a total of 511 individuals. The adult population included consists of 469 individuals (91.8% of the total) and their phenotype distribution is: 348 Pi*ZZ (74.2%), 100 Pi*SZ (21.3%) and 21 carriers of rare variants (4.5%). The most frequent diagnosis is lung disease (74.6%). Patients with chronic obstructive pulmonary disease (COPD) registered in the REDAAT constitute approximately 15% of the expected cases of AATD-related COPD in Spain. Pi*ZZ showed more severe impairment in lung function and younger age at baseline compared with Pi*SZ. The mean decline in FEV1 in the Pi*ZZ subgroup was –23 ml/year (SD:142.8), being –18 ml/year (SD:108.8) in Pi*SZ. Forty-five percent of the Pi*ZZ individuals received augmentation therapy. A total of 61 deaths was recorded.The characteristics of the REDAAT population demonstrate some differential trends compared to other series: distribution of phenotypes, inclusion of children and patients treated with replacement therapy. Patients with the Pi*SZ phenotype were older and had milder lung function impairment. The most important challenge of this registry is to collect good quality long-term data that will allow better understanding of the natural history of the disease in real life.

Analysis of factors associated with decline of FEV1 among community population in urban area of Beijing

To investigate risk factors correlated to the decline of FEV₁among community population in the urban area of Beijing. Subjects no younger than 40 years old were recruited from three communities in the urban area of Beijing. All of them were asked to fill in a questionnaire in regard to general health conditions, past medical history, medication usage, smoking history, etc. FEV₁and FEV6 were measured by Vitalograph COPD-6 spirometer using the standard protocol. Two years after the first visit, questionnaire survey and spirometry were repeated. Four hundred and fifty two subjects fulfilled the inclusion criteria and finished the 2nd visit, with an average age of (58.8 ± 8.6) years, 29% male and 71% female. The mean decline rate of FEV₁in the cohort was (43 ± 114) ml per year. There was no significant difference of mean FEV₁decline between different gender and age groups. A mean decline of FEV₁by (64 ± 125) ml per year was observed in smokers (including former smokers and current smokers) whereas the decline rate in non-smokers was (36 ± 109) ml per year (P = 0.030). There was no significant statistical difference among current smokers, former smokers, passive smokers and subjects who never smoke. A higher decline rate of FEV₁was observed in subjects with a history of COPD or airway hyperreactivity, chronic cough, diabetes, hypertension and coronary heart disease. The difference, however, was not statistically significant. Binary logistic regression was used to screen risk factors affected the FEV₁decline rate between rapid decline (ΔFEV1 ≥ 30 ml/y) and non-rapid decline (ΔFEV1 < 30 ml/y), and found smoking was an independent risk factor of FEV₁decline rate. The mean rate of FEV1 decline in 2.6 years in the surveyed community population in the urban area of Beijing was (43 ± 114) ml per year; Smoking is an independent risk factor of FEV₁decline.