Absolute lung size and the sex difference in breathlessness in the general population.
ABSTRACT: Breathlessness is associated with major adverse health outcomes and is twice as common in women as men in the general population. We evaluated whether this is related to their lower absolute lung volumes.Cross-sectional analysis of the population-based Swedish CardioPulmonarybioImage Study (SCAPIS) Pilot, including static spirometry and diffusing capacity (n = 1,013; 49% women). Breathlessness was measured using the modified Medical Research Council (mMRC) scale and analyzed using ordinal logistic regression adjusting for age, pack-years of smoking, body mass index, chronic airway limitation, asthma, chronic bronchitis, depression and anxiety in all models.Breathlessness was twice as common in women as in men; adjusted odds ratio (OR) 2.20 (95% confidence interval, 1.32-3.66). Lower absolute lung volumes were associated with increased breathlessness prevalence in both men and women. The sex difference in breathlessness was unchanged when adjusting for lung function in %predicted, but disappeared when controlling for absolute values of total lung capacity (OR 1.12; 0.59-2.15), inspiratory capacity (OR 1.26; 0.68-2.35), forced vital capacity (OR 0.84; 0.42-1.66), forced expiratory volume in one second (OR 0.70; 0.36-1.35) or lung diffusing capacity (OR 1.07; 0.58-1.97).In the general population, the markedly higher prevalence of breathlessness in women is related to their smaller absolute lung volumes.
Project description:Peak oxygen uptake (VO2peak) is an indicator of cardiovascular health and a useful tool for risk stratification. Direct measurement of VO2peak is resource-demanding and may be contraindicated. There exist several non-exercise models to estimate VO2peak that utilize easily obtainable health parameters, but none of them includes lung function measures or hemoglobin concentrations. We aimed to test whether addition of these parameters could improve prediction of VO2peak compared to an established model that includes age, waist circumference, self-reported physical activity and resting heart rate. We included 1431 subjects aged 69-77 years that completed a laboratory test of VO2peak, spirometry, and a gas diffusion test. Prediction models for VO2peak were developed with multiple linear regression, and goodness of fit was evaluated. Forced expiratory volume in one second (FEV1), diffusing capacity of the lung for carbon monoxide and blood hemoglobin concentration significantly improved the ability of the established model to predict VO2peak. The explained variance of the model increased from 31% to 48% for men and from 32% to 38% for women (p<0.001). FEV1, diffusing capacity of the lungs for carbon monoxide and hemoglobin concentration substantially improved the accuracy of VO2peak prediction when added to an established model in an elderly population.
Project description:Background:Advanced glycation end-products (AGEs) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the association between AGE accumulation in the skin measured by skin autofluorescence (SAF) and lung function in healthy subjects has not been explored in detail. We use a population-based study of 50-64-year-olds to assess spirometry, diffusing capacity of the lung for carbon monoxide (D LCO) and impulse oscillometry (IOS) in relation to SAF. Methods:Participants with information on SAF, lung function and potential confounding variables were included from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) cohort (spirometry, n=4111; D LCO, n=3889; IOS, n=3970). Linear regression was used to assess changes in lung function (as measured by spirometry (forced expiratory volume in 1?s (FEV1), forced vital capacity (FVC) and FEV1/FVC), D LCO and IOS (resistance measured at 5 (R 5) and 20?Hz (R 20), R 5-R 20, area of reactance, reactance measured at 5?Hz (X- 5), and resonant frequency)) by a 1-sd increase in SAF. Results:FEV1, FVC and D LCO were significantly and inversely associated with SAF after adjustment for potential confounding factors (per 1-sd increase in SAF: FEV1 -0.03?L (95% CI -0.04-?-0.02?L), p<0.001; FVC -0.03?L (95% CI -0.05-?-0.02?L), p<0.001; D LCO -0.07?mmol·min-1·kPa-1 (95% CI -0.11-?-0.03?mmol·min-1·kPa-1), p<0.001). This association was also found in nonsmokers and in non-COPD subjects. Pulmonary reactance (X 5) but not pulmonary resistance (R 5, R 20 and R 5-R 20) was significantly associated with SAF (per 1-sd increase in SAF: X 5 -0.001?kPa·L-1·s (95% CI -0.003-0.00?kPa·L-1·s), p=0.042), which was mirrored in non-COPD patients but not in current nonsmokers. Conclusions:AGE accumulation, as measured by SAF, is significantly associated with lung function decrements indicative of changes in the lung parenchyma.
Project description:Radiographic abnormalities of the pulmonary vessels, such as vascular pruning, are common in advanced airways disease, but it is unknown if pulmonary vascular volumes are related to measures of lung health and airways disease in healthier populations.In 2388 participants of the Framingham Heart Study computed tomography (CT) sub-study, we calculated total vessel volumes and the small vessel fraction using automated CT image analysis. We evaluated associations with measures of lung function, airflow obstruction on spirometry and emphysema on CT. We further tested if associations of vascular volumes with lung function were present among those with normal forced expiratory volume in 1?s and forced vital capacity.In fully adjusted linear and logistic models, we found that lower total and small vessel volumes were consistently associated with worse measures of lung health, including lower spirometric volumes, lower diffusing capacity and/or higher odds of airflow obstruction. For example, each standard deviation lower small vessel fraction (indicating more severe pruning) was associated with a 37% greater odds of obstruction (OR 1.37, 95% CI 1.11-1.71, p=0.004). A similar pattern was observed in the subset of participants with normal spirometry.Lower total and small vessel pulmonary vascular volumes were associated with poorer measures of lung health and/or greater odds of airflow obstruction in this cohort of generally healthy adults without high burdens of smoking or airways disease. Our findings suggest that quantitative CT assessment may detect subtle pulmonary vasculopathy that occurs in the setting of subclinical and early pulmonary and airways pathology.
Project description:BACKGROUND:Health-related quality of life (HRQL) in interstitial lung disease (ILD) patients is impaired. We aimed to identify baseline predictors for HRQL decline within a 12-month observation period. METHODS:We analyzed 194 ILD patients from two German ILD-centers in the observational HILDA study. We employed the disease-specific King's Brief Interstitial Lung Disease questionnaire (K-BILD) with the subdomains 'psychological impact', 'chest symptoms' and 'breathlessness and activities', and the generic EQ-5D Visual Analog Scale (VAS). We evaluated how many patients experienced a clinically meaningful decline in HRQL. Subsequently, we investigated medical and sociodemographic factors as potential predictors of HRQL deterioration. RESULTS:Within the study population (34.0% male, Ø age 61.7) mean HRQL scores hardly changed between baseline and follow up (K-BILD: 52.8 vs. 52.5 | VAS: 60.0 vs. 57.3). On the intra-individual level, 30.4% (n?=?59) experienced a clinically relevant deterioration in K-BILD total score and 35.4% (n?=?68) in VAS. Lower baseline forced vital capacity (FVC) % predicted determined HRQL decline in K-BILD total score (ß-coefficient: - 0.02, p?=?0.007), VAS (ß-coefficient: - 0.03, p?<?0.0001), and in the subdomain 'psychological impact' (ß-coefficient: - 0.02, p?=?0.014). Lower baseline diffusing capacity of carbon monoxide (DLCO) % predicted determined deterioration in 'breathlessness and activities' (ß-coefficient: - 0.04, p?=?0.003) and 'chest symptoms' (ß-coefficient: - 0.04, p?=?0.002). Additionally, increasing age predicted decline in 'psychological impact' (ß-coefficient: 0.06, p?<?0.007). CONCLUSION:Around a third of ILD patients experienced a clinically relevant HRQL deterioration in a 12-month period, which was associated with baseline lung function values in all K-BILD domains. As lung function values are time-dependent variables with possible improvements, in contrast to age and ILD subtype, it, thus, seems important to improve lung function and prevent its decline in order to maintain HRQL on the possibly highest level.
Project description:INTRODUCTION: The purpose of the present study was to systematically review the effect of cyclophosphamide treatment on pulmonary function in patients with systemic sclerosis and interstitial lung disease. METHODS: The primary outcomes were the mean change in forced vital capacity and in diffusing capacity for carbon monoxide after 12 months of therapy in patients treated with cyclophosphamide. RESULTS: Three randomized clinical trials and six prospective observational studies were included for analysis. In the pooled analysis, the forced vital capacity and the diffusing capacity for carbon monoxide predicted values after 12 months of therapy were essentially unchanged, with mean changes of 2.83% (95% confidence interval = 0.35 to 5.31) and 4.56% (95% confidence interval = -0.21 to 9.33), respectively. CONCLUSIONS: Cyclophosphamide treatment in patients with systemic sclerosis-related interstitial lung disease does not result in clinically significant improvement of pulmonary function.
Project description:Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM.We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment--a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period. The primary end point was the difference between the groups in the rate of change (slope) in forced expiratory volume in 1 second (FEV(1)).During the treatment period, the FEV(1) slope was -12±2 ml per month in the placebo group (43 patients) and 1±2 ml per month in the sirolimus group (46 patients) (P<0.001). The absolute between-group difference in the mean change in FEV(1) during the treatment period was 153 ml, or approximately 11% of the mean FEV(1) at enrollment. As compared with the placebo group, the sirolimus group had improvement from baseline to 12 months in measures of forced vital capacity, functional residual capacity, serum vascular endothelial growth factor D (VEGF-D), and quality of life and functional performance. There was no significant between-group difference in this interval in the change in 6-minute walk distance or diffusing capacity of the lung for carbon monoxide. After discontinuation of sirolimus, the decline in lung function resumed in the sirolimus group and paralleled that in the placebo group. Adverse events were more common with sirolimus, but the frequency of serious adverse events did not differ significantly between the groups.In patients with LAM, sirolimus stabilized lung function, reduced serum VEGF-D levels, and was associated with a reduction in symptoms and improvement in quality of life. Therapy with sirolimus may be useful in selected patients with LAM. (Funded by the National Institutes of Health and others; MILES ClinicalTrials.gov number, NCT00414648.).
Project description:The dose-response relationship between glycemic status and lung function has not been thoroughly investigated. We hypothesized that there are continuous and inverse associations between glycemic measures and lung function tests and examined the hypothesis in Japanese adults.We cross-sectionally investigated associations of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) with forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in 3161 adults who participated in a health screening from 2008 to 2011. The study participants included both diabetic and non-diabetic adults. Multiple linear regression analyses were performed to examine the associations.Inverse associations were observed in both sexes, which were attenuated in women after adjustment for multiple variables. A 1% absolute increase in HbA1c was associated with a -52-mL (95% confidence interval [CI] -111 to 8 mL) difference in FVC and a -25-mL (95% CI -75 to 25 mL) difference in FEV1 in women, and a -128-mL (95% CI -163 to -94 mL) difference in FVC and a -73-mL (95% CI -101 to -44 mL) difference in FEV1 in men. A 10-mg/dL increase in FPG was associated with a -11-mL (95% CI -29 to 8 mL) difference in FVC and a -8-mL (95% CI -24 to 7 mL) difference in FEV1 in women, and a -32-mL (95% CI -44 to -21 mL) difference in FVC and a -19-mL (95% CI -28 to -9 mL) difference in FEV1 in men.Inverse associations between glycemic measures and lung function were observed. Men seem more susceptible to the alteration in FVC and FEV1 than women.
Project description:The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease.To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness.Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity. Patients with 3% or greater polymorphonuclear and/or 2% or greater eosinophilic leukocytes on lavage and/or ground-glass opacification on computed tomography were eligible for enrollment.Lavage was performed in 201 individuals, including 141 of the 158 randomized patients. Abnormal cellularity was present in 101 of these cases (71.6%) and defined a population with a higher percentage of men (P = 0.04), more severe lung function, including a worse forced vital capacity (P = 0.003), worse total lung capacity (P = 0.005) and diffusing capacity of the lung for carbon monoxide (P = 0.004), more extensive ground-glass opacity (P = 0.005), and more extensive fibrosis in the right middle lobe (P = 0.005). Despite these relationships, the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year (P = not significant).The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response. Clinical trial registered with www.clinicaltrials.gov (NCT 000004563).
Project description:Higher levels of testosterone have been associated with better lung function in cross-sectional population-based studies. The role of testosterone in lung function in women and in lung function decline in men or women is unclear. We studied 5114 men and 5467 women in the UK Biobank with high-quality spirometry at baseline (2006–2010) and 8.4?years later. We studied cross-sectional associations of total testosterone (TT), calculated free testosterone (cFT), free androgen index (FAI) and sex hormone-binding globulin (SHBG) with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC using linear regression and associations of baseline markers with lung function decline using linear mixed-effects regression. Men with higher levels of TT had higher FEV1 (27.56?mL per interquartile range increase TT, 95% CI 5.43–49.68) and FVC (48.06?mL, 95% CI 22.07–74.06) at baseline. Higher cFT levels were associated with higher FEV1 and FVC among physically active men only. In women, higher FAI and cFT levels were associated with lower lung function at baseline and higher levels of TT, cFT and FAI were associated with slightly attenuated FEV1 and FVC decline. Higher levels of SHBG were associated with better lung function in both sexes but slightly accelerated decline in men. In this population-based sample, higher levels of TT were associated with better lung function in men and higher levels of cFT with better lung function in physically active men. A small attenuation of lung function decline with higher levels of TT, cFT and FAI was seen in women only. Higher levels of testosterone are associated with better lung function in men, especially if physically active, but not in women. A small attenuation of lung function decline with higher testosterone levels is seen in women only.https://bit.ly/382d0xT
Project description:Angiogenesis is a defining pathologic feature of airway remodeling and contributes to asthma severity. Women experience changes in asthma control over the menstrual cycle, a time when vessels routinely form and regress under the control of angiogenic factors. One vital function modulated over the menstrual cycle in healthy women is gas transfer, and this has been related to angiogenesis and cyclic expansion of the pulmonary vascular bed.We hypothesized that changes in gas transfer and the pulmonary vascular bed occur in women with asthma over the menstrual cycle and are associated with worsening airflow obstruction.Twenty-three women, 13 with asthma and 10 healthy control subjects, were evaluated over the menstrual cycle with weekly measures of spirometry, gas transfer, nitric oxide, hemoglobin, factors affecting hemoglobin binding affinity, and proangiogenic factors.Airflow and lung diffusing capacity varied over the menstrual cycle with peak levels during menses that subsequently declined to nadir in early luteal phase. In contrast to healthy women, changes in lung diffusing capacity (DL(CO)) were associated with changes in membrane diffusing capacity and DL(CO) was not related to proangiogenic factors. DL(CO) did not differ between the two groups, although methemoglobin and carboxyhemoglobin were higher in women with asthma than in healthy women.Women with asthma experience cyclic changes in airflow as well as gas transfer and membrane diffusing capacity supportive of a hormonal effect on lung function.