Relationship between frequency, length, and treatment outcome of exacerbations to baseline lung function and lung density in alpha-1 antitrypsin-deficient COPD

Background: Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder involving lungs, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT) also called proteinase inhibitor (PI). Asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with AATD. Objectives: The aim of the study was to evaluate lung function in asthmatic outpatients with mutation in the SERPINA1 gene coding for AAT versus asthmatic subjects without mutation. Methods: We performed the quantitative analysis of the serum concentration of AAT in 600 outpatients affected by mild to moderate asthma from the University Hospital of Parma, Italy. Fifty-seven of them underwent the genetic analysis subsequently; they were subdivided into mutated and non-mutated subjects. All the mutated patients had a heterozygous genotype, except 1 (PI*SS). We assessed the lung function through a flow-sensing spirometer and the small airway parameters through an impulse oscillometry system. Results: The values of forced vital capacity (% predicted) and those of the residual volume to total lung capacity ratio (%) were, respectively, lower and higher in patients mutated versus patients without mutation, showing a significantly greater air trapping (p = 0.014 and p = 0.017, respectively). Moreover, patients with mutation in comparison to patients without mutation showed lower forced expiratory volume in 3 s (% predicted) and forced expiratory volume in 6 s (L) spirometric values, reflecting a smaller airways contribution. Conclusions: In asthmatic patients, heterozygosity for AAT with PI*MZ and PI*MS genotypes was associated with small airway dysfunction and with lung air trapping.

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Lung function and CT lung densitometry in 37- to 39-year-old individuals with alpha-1-antitrypsin deficiency

International Journal of Chronic Obstructive Pulmonary Disease ◽

10.2147/copd.s167497 ◽

2018 ◽

Vol Volume 13 ◽

pp. 3689-3698 ◽

Cited By ~ 3

Author(s):

Behrouz Mostafavi ◽

Sandra Diaz ◽

Eeva Piitulainen ◽

Berend Stoel ◽

Per Wollmer ◽

...

Keyword(s):

Lung Function ◽

Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin ◽

Lung Densitometry

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Health status and lung function in the Swedish alpha 1-antitrypsin deficient cohort, identified by neonatal screening, at the age of 37-40 years

International Journal of Chronic Obstructive Pulmonary Disease ◽

10.2147/copd.s120241 ◽

2017 ◽

Vol Volume 12 ◽

pp. 495-500 ◽

Cited By ~ 12

Author(s):

Eeva Piitulainen ◽

Behrouz Mostafavi ◽

Hanan Tanash

Keyword(s):

Health Status ◽

Lung Function ◽

Neonatal Screening ◽

Alpha 1 Antitrypsin

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Relationship of CT densitometry to lung physiological parameters and health status in alpha-1 antitrypsin deficiency: initial report of a centralised database of the NIHR rare diseases translational research collaborative

BMJ Open ◽

10.1136/bmjopen-2019-036045 ◽

2020 ◽

Vol 10 (6) ◽

pp. e036045

Author(s):

Diana Crossley ◽

James Stockley ◽

Charlotte E Bolton ◽

Nicholas S Hopkinson ◽

Ravi Mahadeva ◽

...

Keyword(s):

Health Status ◽

Lung Function ◽

Lung Disease ◽

Clinical Features ◽

Obstructive Lung Disease ◽

Chronic Obstructive Lung Disease ◽

Chronic Obstructive ◽

Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin

ObjectivesTo establish a database network for the study of alpha-1 antitrypsin deficiency (AATD) and compare the results to CT lung density as the most direct measure of emphysema.DesignA central electronic database was established to permit the upload of anonymised patient data from remote sites. Prospectively collected CT data were recorded onto disc, anonymised, analysed at the coordinating centre and compared with the clinical features of the disease.SettingTertiary referral centres with expertise in the management of AATD focused on academic Biomedical Research Units and Wellcome Clinical Research Facilities.ParticipantsData were collected from 187 patients over 1 year from eight UK academic sites. This included patient demographics, postbronchodilator physiology, health status and CT. Analysis was undertaken at the coordinating centre in Birmingham.ResultsPatient recruitment in the 12 months reached 94% of target (set at 200) covering the whole spectrum of the disease from those with normal lung function to very severe chronic obstructive lung disease. CT scan suitable for analysis was available from 147 (79%) of the patients. CT density, analysed as the threshold for the lowest 15% of lung voxels, showed statistically significant relationships with the objective physiological parameters of lung function as determined by spirometric Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity staging (p<0.001) and carbon monoxide gas transfer (p<0.01). Density also correlated with subjective measures of quality of life (p=0.02).ConclusionsEstablishment of the network for data collection and its transfer was highly successful facilitating future collaboration for the study of this rare disease and its management. CT densitometry correlated well with the objective clinical features of the disease supporting its role as the specific marker of the associated emphysema and its severity. Correlations with subjective measures of health, however, were generally weak indicating other factors play a role.

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