The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: results from the Burden of Obstructive Lung Disease (BOLD) study

Abstract

Background: Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown.

Methods: Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF_25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV₃/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV₁/FVC ≥ LLN).

Results: Almost a fifth of the participants had spirometric SAO (19% for FEF_25-75; 17% for FEV₃/FVC). Using FEF_25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77-2.70), chronic cough (OR = 2.56, 95% CI 2.08-3.15), chronic phlegm (OR = 2.29, 95% CI 1.77-4.05), wheeze (OR = 2.87, 95% CI 2.50-3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11-1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV₃/FVC. Isolated spirometric SAO (10% for FEF_25-75; 6% for FEV₃/FVC), was also associated with respiratory symptoms and cardiovascular disease.

Conclusion: Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF_25-75 and FEV₃/FVC, in addition to traditional spirometry parameters.

Keywords: Cardiovascular disease; Quality of life; Small airways obstruction; Spirometry; Symptoms.

Fig. 1

Pooled estimates for the effect of spirometric SAO measured using FEV₃/FVC (a) and FEF_25-75 (b) on respiratory symptoms in the BOLD study. Spirometric SAO: Small airways obstruction. Overall: spirometric SAO defined as FEV₃/FVC or FEF_25-75 less than the lower limit of normal (LLN). Male/Female: spirometric SAO as FEV₃/FVC or FEF_25-75 < LLN stratified by sex. Isolated spirometric SAO: FEV₃/FVC or FEF_25-75 < LLN with FEV₁/FVC ≥ LLN. Dyspnoea measured according to mMRC Dyspnoea scale: 0–1 = minimal/no breathlessness, ≥ 2 = significant breathlessness. Chronic cough: cough on most days for 3 months each year. Chronic Phlegm: Phlegm on most days 3 months each year. Wheeze: Wheezing or whistling in the chest at any time in the last 12 months. OR 95% CI: odds ratio with 95% confidence intervals. I² values of 0%, 25%, 50%, and 75% considered no, low, moderate, and high heterogeneity. Covariates in the adjusted model: sex, education level, body mass index, smoking status, accumulated cigarette pack-years, passive smoking, occupational exposure to dust, use of solid fuels for cooking/heating for > 6 months in a lifetime, reported doctor-diagnosed or history of tuberculosis, spirometric restriction, family history of COPD, and for Dyspnoea addition of CVD. The following sites could not be included in the analysis either due to a low number of participants reporting respiratory symptoms or singularity in the data: Benin (Sémé-Kpodji), Norway (Bergen), Malawi (Blantyre), China (Guangzhou), Germany (Hannover), Cameroon (Limbe), India (Mumbai) (Mysore), Austria (Salzburg), Tunisia (Sousse), Australia (Sydney), Albania (Tirana), Sweden (Uppsala)

Fig. 2

Pooled estimates for the effect of spirometric SAO measured using FEV₃/FVC (a) and FEF_25-75 (b) on cardiometabolic disease in the BOLD study. Spirometric SAO: Small airways obstruction. Overall: spirometric SAO defined as FEV₃/FVC or FEF_25-75 less than the lower limit of normal (LLN). Male/Female: spirometric SAO as FEV₃/FVC or FEF_25-75 < LLN stratified by sex. Isolated spirometric SAO: FEV₃/FVC or FEF_25-75 < LLN with FEV₁/FVC ≥ LLN. Cardiovascular disease: self-reported history of heart disease or stroke. OR (95% CI): odds ratio with 95% confidence intervals. I² values of 0%, 25%, 50%, and 75% considered no, low, moderate, and high heterogeneity. Covariates in the adjusted model: sex, education level, body mass index, smoking status, accumulated cigarette pack-years and spirometric restriction. The following sites could not be included in the analysis either due to a low number of participants reporting co-morbidity or singularity in the data: For CVD; Malawi (Blantyre), Malawi (Chikwawa), Nigeria (Ife), Cameroon (Limbe), India (Mysore), India (Kashmir), Malaysia (Penang), Sudan (Gezeira), Morocco (Fes), China (Guangzhou), Jamaica, Trinidad & Tobago (Port of Spain), Saudi Arabia (Riyadh), and Albania (Tirana). For Hypertension; Benin (Sémé-Kpodji), Malawi (Chikwawa), and Sudan (Gezeira). For diabetes; India (Pune), Malawi (Chikwawa), Morocco (Fes), China (Guangzhou), Nigeria (Ife), Kyrgyzstan (Naryn), Cameroon (Limbe), Philippines (Manilla), India (Mumbai), Malaysia (Penang)

Fig. 3

Pooled estimates for the effect of spirometric SAO measured using FEV₃/FVC (a) and FEF_25-75 (b) on physical and mental quality of life in the BOLD study. Spirometric SAO: Small airways obstruction. Overall: spirometric SAO defined as FEV₃/FVC or FEF_25-75 less than the lower limit of normal (LLN). Male/Female: spirometric SAO as FEV₃/FVC or FEF_25-75 < LLN stratified by sex. Isolated spirometric SAO: FEV₃/FVC or FEF_25-75 < LLN with FEV₁/FVC ≥ LLN. Physical and mental QoL measured using the SF-12 questionnaire. Negative regression coefficient indicates that having SAO is associated with a reduction in SF-12 score in comparison to not having SAO. I² values of 0%, 25%, 50%, and 75% considered no, low, moderate, and high heterogeneity. Covariates in the adjusted model: sex, education level, body mass index, smoking status, accumulated cigarette pack-years, passive smoking, occupational exposure to dust, use of solid fuels for cooking/heating for > 6 months in a lifetime, reported doctor-diagnosed or history of tuberculosis, spirometric restriction, family history of COPD, CVD, hypertension, and diabetes. Estimates based on the analysis of 31 sites, the following sites could not be included in the analysis either due to low response rate to the questionnaire; Turkey (Adana) and China (Guangzhou) or where QoL was measured using a different tool; Benin (Sémé-Kpodji), Cameroon (Limbe), Jamaica, Kyrgyzstan (Chui), Kyrgyzstan (Naryn), Malaysia (Penang), Pakistan (Karachi), Sri Lanka (Colombo)