Maximal mid-expiratory flow detects early lung disease in α(1)-antitrypsin deficiency.

Pathological studies suggest that loss of small airways precedes airflow obstruction and emphysema in chronic obstructive pulmonary disease (COPD). Not all α1-antitrypsin deficiency (AATD) patients develop COPD, and measures of small airways function might be able to detect those at risk.Maximal mid-expiratory flow (MMEF), forced expiratory volume in 1 s (FEV1), ratio of FEV1/forced vital capacity (FVC), health status, presence of emphysema (computed tomography (CT) densitometry) and subsequent decline in FEV1 were assessed in 196 AATD patients.FEV1/FVC, FEV1 % predicted and lung densitometry related to MMEF % pred (r2=0.778, p<0.0001; r2=0.787, p<0.0001; r2=0.594, p<0.0001, respectively) in a curvilinear fashion. Patients could be divided into those with normal FEV1/FVC and MMEF (group 1), normal FEV1/FVC and reduced MMEF (group 2) and those with spirometrically defined COPD (group 3). Patients in group 2 had worse health status than group 1 (median total St George's Respiratory Questionnaire (SGRQ) 23.15 (interquartile range (IQR) 7.09-39.63) versus 9.67 (IQR 1.83-22.35); p=0.006) and had a greater subsequent decline in FEV1 (median change in FEV1 -1.09% pred per year (IQR -1.91-0.04% pred per year) versus -0.04% pred per year (IQR -0.67-0.03% pred per year); p=0.007).A reduction in MMEF is an early feature of lung disease in AATD and is associated with impaired health status and a faster decline in FEV1.

Stockley JA ，Ismail AM ，Hughes SM ，Edgar R ，Stockley RA ，Sapey E ... -  《-》

Structural features on quantitative chest computed tomography of patients with maximal mid-expiratory flow impairment in a normal lung function population.

Maximal mid-expiratory flow (MMEF) is an earlier predictor of chronic obstructive pulmonary disease (COPD) development than forced expiratory volume in 1 s (FEV1). Changes of lung structure in patients with MMEF impairment only is still not clear. Therefore, this study aimed to investigate the structural features of patients with decreased MMEF by quantitative computed tomography (QCT) and develop a predictive model for predicting patients with reduced MMEF in normal lung function population. In this study, 131 patients with normal spirometry results and available volumetric chest CT images were enrolled and divided into the reduced MMEF group (FEV1/forced expiratory vital capacity (FEV1/FVC) > 0.7, FEV1% predictive values (FEV1%pred) > 80%, MMEF%pred < 80%, n = 52) and the normal MMEF group (FEV1/FVC > 0.7, FEV1%pred > 80%, MMEF%pred ≥ 80%, n = 79). The emphysema, small airway disease and medium-size airway parameters were measured by a commercial software. The differences were investigated in clinical features, spirometrical parameters and QCT parameters between the two groups. A nomogram model was constructed based on the results of the multivariable logistic regression model. Spearman's correlation coefficients were calculated between QCT measurements and spirometrical parameters. There were more males in reduced MMEF group than normal group (P < 0.05). Lung parenchyma parameter (PRMEmph) and airway-related parameters (functional small airway disease (PRMfSAD), luminal area of fifth- and sixth- generation airway (LA5, LA6) were significantly different between the reduced MMEF group and the normal group (20.2 ± 17.4 vs 9.4 ± 6.7, 3.4 ± 3.5 vs 1.9 ± 2.0, 12.2 ± 2.5 vs 13.7 ± 3.4, 7.7 ± 2.4 vs 8.9 ± 2.8, respectively, all P < 0.01). After multivariable logistical regression, only sex (odds ratio [OR]: 2.777; 95% confidence interval [CI]:1.123-3.867), PRMfSAD (OR:1.102, 95%CI:1.045-1.162) and LA6 (OR:0.650, 95%CI:0.528-0.799) had significant differences between the two groups (P < 0.05) and a model incorporating with the three indicators was constructed (area under curve, 0.836). Correlation analysis showed MMEF%pred had mild to moderate correlation with airway-related measurements. In normal lung function population, patients with reduced MMEF have potential medium-size and small airway changes, and MMEF%pred is significantly associated with airway-related CT parameters. The nomogram incorporating with sex, PRMfSAD and LA6 has good predictive value and offers more objective evidences in a group with reduced MMEF.

Yang Y ，Ge H ，Lu J ，Huang X ，Wang K ，Jin L ，Qi L ，Li M ... -  《BMC Pulmonary Medicine》

[Study of the clinical phenotype of symptomatic chronic airways disease by hierarchical cluster analysis and two-step cluster analyses].

Ning P ，Guo YF ，Sun TY ，Zhang HS ，Chai D ，Li XM ... -  《-》

Decline in FEV(1) and hospitalized exacerbations in individuals with severe alpha-1 antitrypsin deficiency.

Hiller AM ，Piitulainen E ，Jehpsson L ，Tanash H ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

Exacerbations and duration of smoking abstinence are associated with the annual loss of FEV(1) in individuals with PiZZ alpha-1-antitrypsin deficiency.

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that is associated with a higher risk of chronic obstructive pulmonary disease (COPD) and emphysema. The annual declines in lung function (FEV1) and transfer factor of the lung for carbon monoxide (TLCO) predict all-cause mortality. We investigated the longitudinal follow-up data over 11 years (mean follow-up period of 4.89 years) from the German AATD registry and analyzed the relationship between annual loss of FEV1 and TLCO and sex, age, body mass index (BMI), nicotine consumption, occupational dust exposure, St. George's Respiratory Questionnaire (SGRQ) score, baseline FEV1 or TLCO, alpha-1-antitrypsin (AAT) serum level, exacerbation frequency and the duration of smoking abstinence by multiple linear generalized estimating equations models (GEE-models). We evaluated the data of 100 individuals with post-bronchodilator FEV1 measurements and from 116 individuals with TLCO measurements. The mean overall decline was -54.06 ± 164.62 ml/year in FEV1 and -0.17 ± 0.70 mmol/min/kPa/year in TLCO. Accelerated deterioration of FEV1 was associated with occupational dust exposure (p = 0.026), shorter duration of smoking abstinence (p = 0.008), higher baseline FEV1 (p = 0.003), higher annual exacerbation frequency (p = 0.003) and higher frequency of glucocorticoids intake (p = 0.004). Furthermore, patients with an elevated decline in TLCO showed significant impaired health-related quality of life at baseline (p = 0.039) and lower AAT serum levels (p < 0.001) in multivariate analysis. Annual decline in FEV1 is related to the exacerbation rate, occupational dust exposure and the duration of smoking abstinence.

Fähndrich S ，Bernhard N ，Lepper PM ，Vogelmeier C ，Seibert M ，Wagenpfeil S ，Bals R ... -  《-》