Rate of progression of lung function impairment in alpha1-antitrypsin deficiency.

The aim of the present study was to identify alpha(1)-antitrypsin (alpha(1)-AT)-deficient patients who had rapidly progressive disease. PiZ patients (n = 101) underwent annual lung function measurements over a 3-yr period, and the results were related to factors that may influence decline. The mean annual decline in forced expiratory volume in 1 s (FEV(1)) was 49.9 mL. The greatest FEV(1) decline occurred in the moderate severity group (FEV(1) 50-80% of the predicted value), with a mean annual decline of 90.1 mL, compared with 8.1 mL in the very severe group (FEV(1) <30% pred). However, annual decline in transfer coefficient of the lung for carbon monoxide (K(CO)) was greatest in the severe and very severe groups. When the whole group was divided into tertiles of FEV(1) decline, the fast tertile compared with the slow tertile had more patients with bronchodilator reversibility (BDR) (73 versus 41%; p = 0.010), more males (79 versus 56%; p = 0.048) and lower body mass index (BMI) (24.0 versus 26.1; p = 0.042). Logistic regression analyses confirmed that FEV(1) decline was independently associated with BMI, BDR, exacerbation rate and high physical component 36-item short-form health survey scores. In PiZ alpha(1)-AT-deficient patients, FEV(1) decline was greatest in moderate disease, unlike K(CO) decline, which was greatest in severe disease. The FEV(1) decline showed associations with BDR, BMI, sex and exacerbation rate.

Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant.

BACKGROUND: Exposure to metal working fluid (MWF) has been associated with outbreaks of extrinsic allergic alveolitis (EAA) in the USA, with bacterial contamination of MWF being a possible cause, but is uncommon in the UK. Twelve workers developed EAA in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. The study had three aims: (1) to measure the extent of the outbreak by identifying other workers who may have developed EAA or other work-related respiratory diseases; (2) to provide case detection so that those affected could be treated; and (3) to provide epidemiological data to identify the cause of the outbreak. METHODS: The outbreak was investigated in a three-phase cross-sectional survey of the workforce. In phase I a respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. In phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481 (94.4%) responded and 48/50 (96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). In phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. RESULTS: 87 workers (10.4% of the workforce) met case definitions for occupational lung disease, comprising EAA (n = 19), occupational asthma (n = 74) and humidifier fever (n = 7). 12 workers had more than one diagnosis. The peak onset of work-related breathlessness was Spring 2003. The proportion of workers affected was higher for those using MWF from a large sump (27.3%) than for those working all over the manufacturing area (7.9%) (OR = 4.39, p<0.001). Two workers had positive specific provocation tests to the used but not the unused MWF solution. CONCLUSIONS: Extensive investigation of the outbreak of EAA detected a large number of affected workers, not only with EAA but also occupational asthma. This is the largest reported outbreak in Europe. Mist from used MWF is the likely cause. In workplaces using MWF there is a need to carry out risk assessments, to monitor and maintain fluid quality, to control mist and to carry out respiratory health surveillance.

Predictors of mortality in alpha1-antitrypsin deficiency.

BACKGROUND: Lung density measurements by computed tomography have previously been found to be a more sensitive indicator of disease progression in emphysema of alpha(1)-antitrypsin deficiency than lung function measurements. The aim of this study was to investigate the predictive potential of several parameters, including CT scanning, for mortality in patients with severe alpha(1)-antitrypsin deficiency. METHODS: Over a 5 year period, 256 patients with alpha(1)-antitrypsin deficiency (PiZ phenotype) were assessed, of whom 254 underwent lung function testing and 197 had thoracic CT scans. Lung function, CT scans, health status (St George's Respiratory Questionnaire, SGRQ), and other clinical data of survivors and non-survivors were compared and these parameters were applied to survival analyses. RESULTS: There were 22 deaths in this patient cohort, 10 of which were classified as "respiratory" deaths. Baseline lung function parameters (forced expiratory volume in 1 second (FEV(1)), carbon monoxide transfer coefficient (KCO)), and CT scores were significantly lower in the non-survivors than in the survivors. 170 of the 256 patients had complete data for entry into multiple regression analyses (Cox proportional hazards model). In the univariate analysis, upper zone expiratory scan had the best association with all cause (p = 0.001) and respiratory mortality (p<0.001), whereas FEV(1) (p = 0.158 all cause, 0.015 respiratory) and KCO (p = 0.002 all cause, 0.012 respiratory) had poorer associations with mortality. Only age gave further independent predictive information regarding all cause or respiratory mortality when the CT scan was entered into the survival analyses. CONCLUSIONS: CT scanning predicts respiratory and all cause mortality in alpha(1)-antitrypsin deficiency and appears to be superior to lung function parameters, especially FEV(1).