Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis

Background

Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively. We examined whether changes in trough forced expiratory volume in 1 second (FEV₁) are correlated with changes in patient-reported outcomes.

Methods

Pooled data from three indacaterol studies (n = 3313) were analysed. Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St. George''s Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV₁. Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.

Results

With increasing positive ΔFEV₁, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001). Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95. At 26 weeks, a 100 ml increase in FEV₁ was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease). Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV₁ and outcomes.

Conclusions

These results suggest that larger improvements in FEV₁ are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00393458","term_id":"NCT00393458"}}NCT00393458, {"type":"clinical-trial","attrs":{"text":"NCT00463567","term_id":"NCT00463567"}}NCT00463567, and {"type":"clinical-trial","attrs":{"text":"NCT00624286","term_id":"NCT00624286"}}NCT00624286     

Gene promoter methylation is associated with lung function in the elderly: The normative aging study

Lung function is a strong predictor of mortality. While inflammatory markers have been associated with lung function decrease, pathways are still poorly understood and epigenetic changes may participate in lung function decline mechanisms. We studied the cross-sectional association between DNA methylation in nine inflammatory genes and lung function in a cohort of 756 elderly men living in the metropolitan area of Boston. Participants donated a blood sample for DNA methylation analysis and underwent spirometry at each visit every 3 to 5 y from 1999–2006. We used separate multivariate mixed effects regression models to study the association between each lung function measurement and DNA methylation within each gene. Decreased CRAT, F3 and TLR2 methylation was significantly associated with lower lung function. One interquartile range (IQR) decrease in DNA methylation was associated with lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁), respectively by 2.94% (p < 10^?4) and 2.47% (p < 10^?3) for F3, and by 2.10% (p < 10^?2) and 2.42% (p < 10^?3) for TLR2. Decreased IFNγ and IL6 methylation was significantly associated with better lung function. One IQR decrease in DNA methylation was associated with higher FEV₁ by 1.75% (p = 0.02) and 1.67% (p = 0.05) for IFNγ and IL6, respectively. These data demonstrate that DNA methylation may be part of the biological processes underlying the lung function decline and that IFNγ and IL6 may have ambivalent roles through activation of negative feedback.     

Impaired lung function is associated with obesity and metabolic syndrome in adults

Objective: Impaired lung function is associated with obesity and insulin resistance. In this study, we investigated the relationship between metabolic syndrome and impaired lung function in adults. Research Methods and Procedures: A total of 46,514 subjects 20 years and over (21,669 men and 24,845 women, mean age = 37.3 ± 11.2 and 37.0 ± 11.3 years, respectively) were recruited from four nationwide MJ Health Screening Centers in Taiwan from 1998 to 2000. Metabolic syndrome was defined using the National Cholesterol Education Panel (NCEP) metabolic syndrome criteria or America Heart Association/National Heart Lung Blood Institute (AHA/NHLBI) criteria. The relationship between metabolic syndrome and lung function test was examined using multivariate logistic regression analysis. Results: The prevalence of impaired lung function was 11.1% in men and 14.0% in women. The prevalence of metabolic syndrome was 5.8% using NCEP criteria and 12.8% using AHA/NHLBI criteria. In multivariate logistic regression analysis with adjustment for age, gender, BMI, smoking, alcohol drinking, and physical activity, restrictive lung impairment was independently associated with increased risk of having metabolic syndrome (p < 0.01, odds ratios = 1.221 using NCEP criteria and 1.150 using AHA/NHLBI criteria). Discussion: Obesity and metabolic syndrome were associated with impaired lung function in adults in Taiwan. Our results imply that obesity and insulin resistance may be the common pathways underlying lung function impairment and metabolic syndrome. Moreover, lung function test may be applied as an additional evaluation for metabolic syndrome in a clinical setting.     

Respiratory Sinus Arrhythmia Biofeedback Therapy for Asthma: A Report of 20 Unmedicated Pediatric Cases Using the Smetankin Method

This multiple case study describes pulmonary function changes in 20 asthmatic children from 30 consecutive cases undergoing biofeedback training for increasing the amplitude of respiratory sinus arrhythmia (RSA). The Smetankin protocol was used, which, in addition to RSA biofeedback, includes instructions in relaxed abdominal pursed-lips breathing. Ten individuals were excluded, including 6 who had been taking asthma medication, 2 who developed viral infections during the treatment period, and 2 who dropped out prior to completing treatment. Patients each received 13 to 15 sessions of training. Asthma tended to be mild, with mean spirometric values close to normal levels. Nevertheless, significant improvements were noted in 2 spirometry measures taken during forced expiratory maneuvers from maximum vital capacity: FEV₁ and FEF50. These preliminary uncontrolled data suggest that the Smetankin protocol warrants further evaluation as a nonpharmacological psychophysiological treatment for this condition, although these data could not definitively prove that the method is effective.     

Resting metabolic rate and lung function in fasted and fed rough-toothed dolphins,Steno bredanensis

We measured resting metabolic rate (RMR), tidal volume (V_T), breathing frequency (f_R), respiratory flow, and end-expired gases in rough-toothed dolphins (Steno bredanensis) housed in managed care after an overnight fast and 1–2 hr following a meal. The measured average (± standard deviation) V_T (4.0 ± 1.3 L) and f_R (1.9 ± 1.0 breaths/min) were higher and lower, respectively, as compared with estimated values from both terrestrial and aquatic mammals, and the average V_T was 43% of the estimated total lung capacity. The end-expired gas levels suggested that this species keep alveolar O₂ (10.6% or 80 mmHg) and CO₂ (7.6% or 57 mmHg), and likely arterial gas tensions, low and high, respectively, to maximize efficiency of gas exchange. We show that following an overnight fast, the RMR (566 ± 158 ml O₂/min) was 1.8 times the estimated value predicted by Kleiber for terrestrial mammals of the same size. We also show that between 1 and 2 hr after ingestion of a meal, the metabolic rate increases an average of 29% (709 ± 126 ml O₂/min). Both body mass (M_b) and f_R significantly altered the measured RMR and we propose that both these variables should be measured when estimating energy use in cetaceans.     

A comparative analysis of biomass and clean fuel exposure on pulmonary function during cooking among rural women in Tamilnadu,India

It is of interest to document data on the comparative analysis of biomass and clean fuel exposure on pulmonary function during cooking among rural women. The study consisted of 100 biomass and 100 LPG fuel using women with no smoking habits and other related illness Parameters such as FVC, FEV1, FEV1/FVC, PEFR, FEF25-75%were obtained using the computerized spirometry to assess the pulmonary function in these subjects. The collected data were analyzed using the Student t-test method and Pearson correlation. The exposure index for biomass fuel users is 69.78±27.25 showing high exposure duration during cooking. The parameters for pulmonary functions significantly declined in FVC (42.34±13.6), FEV1 (45.55±15.98), PEFR (34.11±14.78) and FEF25-75% (45.56±23.00) for biomass fuel user. However, this is not true for FEV1/FVC ratio (107.56±16.9). The increase in PFT suggests the restrictive and obstructive patterns of pulmonary diseases. There was a negative correlation between increased duration of cooking and the value of FEV1/FVC (r = -0.2961), FEF25-75% (r = -0.3519) and PEFR (r = -0.2868). Thus, the deformation of pulmonary function due to extended exposure of biomass fuel for cooking women in rural Tamilnadu is shown using parameter features such as high exposure index, overcrowded area and improper ventilated houses.