Comparison among populations with severe and intermediate alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease.

BACKGROUND: Severe alpha1-antitrypsin (AAT) deficiency (AATD) is associated with a high risk of airflow obstruction and emphysema. The risk of lung disease in those with intermediate AAT deficiency is unclear. Our aims were to compare pulmonary function, time of onset of symptoms, and indicators of quality of life among patients with severe AATD (PI*ZZ), patients with intermediate AATD (PI*MZ) from the Italian Registry of AATD with a chronic obstructive pulmonary disease (COPD) cohort of patients without AATD (PI*MM). METHODS: We considered a total of 613 patients: 330 with the PI*ZZ genotype, 183 with the PI*MZ genotype and 100 with the PI*MM genotype. Radiological exams, pulmonary function test, and measurement of quality of life have been performed on all cohorts of patients. RESULTS: The three populations differ significantly in terms of age at COPD/AATD diagnosis (P=0.00001), respiratory function (FEV1, FVC, DLCO P<0.001), quality of life (P=0.0001) and smoking history (P<0.0001). PI*ZZ genotype had 24.9 times a higher likelihood of developing airflow obstruction. The MZ genotype is not associated with a significant early risk of airflow obstruction. CONCLUSIONS: The comparison of populations with PI*ZZ, MZ and MM genotypes allows to delineate the role of alpha1-antitrypsin deficiency on respiratory function and on the impact on quality of life, in relation to other risk factors. These results highlight the crucial role of primary and secondary prevention on smoking habits in PI*MZ subjects and the importance of an early diagnosis.

Bacterial load and inflammatory response in sputum of alpha-1 antitrypsin deficiency patients with COPD.

Background: Airway inflammation may drive the progression of chronic obstructive pulmonary disease (COPD) associated with alpha-1 antitrypsin deficiency (AATD), but the relationship between airway microbiota and inflammation has not been investigated. Methods: We studied 21 non-treated AATD (AATD-noT) patients, 20 AATD-COPD patients under augmentation therapy (AATD-AT), 20 cigarette smoke-associated COPD patients, 20 control healthy smokers (CS) and 21 non-smokers (CON) with normal lung function. We quantified sputum inflammatory cells and inflammatory markers (IL-27, CCL3, CCL5, CXCL8, LTB4, MPO) by ELISA, total bacterial load (16S) and pathogenic bacteria by qRT-PCR. Results: AATD-AT patients were younger but had similar spirometric and DLCO values compared to cigarette smoke-associated COPD, despite a lower burden of smoking history. Compared to cigarette smoke-associated COPD, AATD-noT and AATD-AT patients had lower sputum neutrophil levels (p=0.0446, p=0.0135), total bacterial load (16S) (p=0.0081, p=0.0223), M. catarrhalis (p=0.0115, p=0.0127) and S. pneumoniae (p=0.0013, p=0.0001). Sputum IL-27 was significantly elevated in CS and cigarette smoke-associated COPD. AATD-AT, but not AATD-noT patients, had IL-27 sputum levels (pg/ml) significantly lower than COPD (p=0.0297) and these positively correlated with FEV1% predicted values (r=0.578, p=0.0307). Conclusions: Compared to cigarette smoke-associated COPD, AATD-AT (COPD) patients have a distinct airway inflammatory and microbiological profile. The decreased sputum bacterial load and IL-27 levels in AATD-AT patients suggests that augmentation therapy play a role in these changes.

Autonomic cardiovascular regulation in subjects with acute mountain sickness.

The aims of this study were 1) to evaluate whether subjects suffering from acute mountain sickness (AMS) during exposure to high altitude have signs of autonomic dysfunction and 2) to verify whether autonomic variables at low altitude may identify subjects who are prone to develop AMS. Forty-one mountaineers were studied at 4,559-m altitude. AMS was diagnosed using the Lake Louise score, and autonomic cardiovascular function was explored using spectral analysis of R-R interval and blood pressure (BP) variability on 10-min resting recordings. Seventeen subjects (41%) had AMS. Subjects with AMS were older than those without AMS (P < 0.01). At high altitude, the low-frequency (LF) component of systolic BP variability (LF(SBP)) was higher (P = 0.02) and the LF component of R-R variability in normalized units (LF(RR)NU) was lower (P = 0.001) in subjects with AMS. After 3 mo, 21 subjects (43% with AMS) repeated the evaluation at low altitude at rest and in response to a hypoxic gas mixture. LF(RR)NU was similar in the two groups at baseline and during hypoxia at low altitude but increased only in subjects without AMS at high altitude (P < 0.001) and did not change between low and high altitude in subjects with AMS. Conversely, LF(SBP) increased significantly during short-term hypoxia only in subjects with AMS, who also had higher resting BP (P < 0.05) than those without AMS. Autonomic cardiovascular dysfunction accompanies AMS. Marked LF(SBP) response to short-term hypoxia identifies AMS-prone subjects, supporting the potential role of an exaggerated individual chemoreflex vasoconstrictive response to hypoxia in the genesis of AMS.

Pulmonary extravascular fluid accumulation in recreational climbers: a prospective study.

BACKGROUND: High altitude pulmonary oedema (HAPE) that is severe enough to require urgent medical care is infrequent. We hypothesised that subclinical HAPE is far more frequent than suspected during even modest climbs of average effort. METHODS: We assessed 262 consecutive climbers of Monte Rosa (4559 m), before ascent and about 24 h later on the summit 1 h after arriving, by clinical examination, electrocardiography, oximetry, spirometry, carbon monoxide transfer, and closing volume. A chest radiograph was taken at altitude. FINDINGS: Only one climber was evacuated for HAPE, but 40 (15%) of 262 climbers had chest rales or interstitial oedema on radiograph after ascent. Of 37 of these climbers, 34 (92%) showed increased closing volume. Of the 197 climbers without oedema, 146 (74%) had an increase in closing volume at altitude. With no change in vital capacity, forced expiratory volume in 1 s and forced expiratory flow at 25-75% of forced vital capacity increased slightly at altitude, without evidence of oedema. If we assume that an increased closing volume at altitude indicates increased pulmonary extravascular fluid, our data suggest that three of every four healthy, recreational climbers have mild subclinical HAPE shortly after a modest climb. INTERPRETATION: The risk of HAPE might not be confined to a small group of genetically susceptible people, but likely exists for most climbers if the rate of ascent and degree of physical effort are great enough, especially if lung size is normal or low.