Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry.

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).

Dual-energy Computed Tomographic Pulmonary Angiography Accurately Estimates Lobar Perfusion Before Lung Volume Reduction for Severe Emphysema.

PURPOSE: To assess if dual-energy computed tomographic pulmonary angiography (DECTPA) derived lobar iodine quantification can provide an accurate estimate of lobar perfusion in patients with severe emphysema, and offer an adjunct to single-photon emission CT perfusion scintigraphy (SPECT-PS) in assessing suitability for lung volume reduction (LVR). MATERIALS AND METHODS: Patients with severe emphysema (forced expiratory volume in 1 s <49% predicted) undergoing evaluation for LVR between May 2018 and April 2020 imaged with both SPECT-PS and DECTPA were included in this retrospective study. DECTPA perfused blood volume maps were automatically segmented and lobar iodine mass was estimated and compared with lobar technetium (Tc99m) distribution acquired with SPECT-PS. Pearson correlation and Bland-Altman analysis were used for intermodality comparison between DECTPA and SPECT-PS. Univariate and adjusted multivariate linear regression were modelled to ascertain the effect sizes of possible confounders of disease severity, sex, age, and body mass index on the relationship between lobar iodine and Tc99m values. Effective radiation dose and adverse reactions were recorded. RESULTS: In all, 123 patients (64.5±8.8 y, 71 men; mean predicted forced expiratory volume in 1 s 32.1 ±12.7%,) were eligible for inclusion. There was a linear relationship between lobar perfusion values acquired using DECTPA and SPECT-PS with statistical significance ( P <0.001). Lobar relative perfusion values acquired using DECTPA and SPECT-PS had a consistent relationship both by linear regression and Bland-Altman analysis (mean bias, -0.01, mean r2 0.64; P <0.0001). Individual lobar comparisons demonstrated moderate correlation ( r =0.79, 0.78, 0.84, 0.78, 0.8 for the right upper, middle, lower, left upper, and lower lobes, respectively, P <0.0001). The relationship between lobar iodine and Tc99m values was not significantly altered after controlling for confounders including symptom and disease severity, age, sex, and body mass index. CONCLUSIONS: DECTPA provides an accurate estimation of lobar perfusion, showing good agreement with SPECT-PS and could potentially streamline preoperative assessment for LVR.

Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies.

BACKGROUND: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. METHODS: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. FINDINGS: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001). INTERPRETATION: If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity. FUNDING: The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme.

Combined Impact of Smoking and Early-Life Exposures on Adult Lung Function Trajectories.

RATIONALE: Both adverse early-life exposures and adult smoking can negatively influence adult lung function trajectory, but few studies consider how the impact of early-life exposures may be modified by subsequent smoking. METHODS: The Medical Research Council National Survey of Health and Development is a nationally representative cohort, initially of 5,362 individuals, followed since enrollment at birth in March 1946. Using data collected prospectively across life and multilevel modeling, we investigated how the relationships between early-life exposures (infant lower respiratory infection, manual social class, home overcrowding, and pollution exposure) and FEV1 and FVC trajectories between ages 43 and 60-64 years were influenced by smoking behavior. MEASUREMENTS AND MAIN RESULTS: Among 2,172 individuals, there were synergistic interactions of smoking with infant respiratory infection (P = 0.04) and early-life home overcrowding (P = 0.009), for FEV1 at 43 years. Within smoker-stratified models, there were FEV1 deficits among ever-smokers associated with infant lower respiratory infection (-108.2 ml; P = 0.001) and home overcrowding (-89.2 ml; P = 0.002), which were not evident among never-smokers (-15.9 ml; P = 0.69 and -13.7 ml; P = 0.70, respectively). FVC modeling, including 1,960 individuals, yielded similar results. FEV1 decline was greater in smokers (P < 0.001), but there was no effect of any early-life exposure on FEV1 decline. Neither smoking nor early-life exposures were associated with FVC decline. CONCLUSIONS: Besides accelerating adult FEV1 decline, cigarette smoking also modifies how early-life exposures impact on both midlife FEV1 and FVC. These findings are consistent with smoking impairing pulmonary development during adolescence or early adulthood, thereby preventing catch-up from earlier acquired deficits.

The Presence of Chronic Mucus Hypersecretion across Adult Life in Relation to Chronic Obstructive Pulmonary Disease Development.

RATIONALE: Chronic mucus hypersecretion (CMH) is common among smokers and is associated with chronic obstructive pulmonary disease development and progression. OBJECTIVES: To understand how the relationships between smoking, CMH, and chronic obstructive pulmonary disease develop during adult life, and facilitate earlier disease detection and intervention. METHODS: We analyzed data on CMH, smoking, and lung function prospectively collected by the Medical Research Council National Survey of Health and Development, a nationally representative British cohort followed since birth in 1946. We analyzed the longitudinal relationships between smoking and CMH, how symptoms during life related to airflow limitation at 60-64 years, and how CMH duration between ages 43 and 60-64 years related to concurrent FEV1 decline. MEASUREMENTS AND MAIN RESULTS: From 5,362 individuals enrolled at birth, 4,427 contributed data between ages 20 and 64 years (52% male; 63% ever-smoker). Among smokers CMH prevalence escalated between ages 36 and 43 from 7.6 ± 2.0% to 13.0 ± 2.6%. At these ages, symptoms were associated with a higher risk of subsequent airflow limitation (odds ratio [95% confidence interval], 3.70 [1.62-8.45] and 4.11 [1.85-9.13], respectively). Across adult life, CMH followed a dynamic remitting-relapsing course. Symptom prevalence following smoking cessation returned to levels seen among never-smokers. The longer CMH was present across three occasions (ages 43, 53, and 60-64 yr), the greater the concurrent FEV1 decline, corresponding to an additional decrement of 3.6 ± 2.5 ml/yr per occasion that CMH was present (P = 0.005). CONCLUSIONS: CMH among middle-aged smokers represents an early developmental phase of chronic obstructive pulmonary disease. Smoking-related CMH usually resolves following smoking cessation but the longer its duration the greater the FEV1 lost, suggesting the course of CMH across adult life may reflect the underlying course of airway disease activity.