Lung distensibility and airway function in intermediate alpha 1-antitrypsin deficiency (Pi MZ).

Tattersall, Susan F.; Pereira, Rose Petrik; Hunter, D; Blundell, Gillian; Pride, N. B.

doi:10.1136/thx.34.5.637

Cited by 32 publications

(10 citation statements)

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“…As several authors [23,31,34,36] have repeatedly pointed out, the simpler tests cannot, in all cases, accurately discriminate between PiMZ and PiMM individuals. It is well-known that asymptomatic individuals showing normal conventional tests of pulmonary function may have significant degrees of mechanical abnormality.…”

Section: Discussionmentioning

confidence: 99%

“…Large surveys of various populations (from a community or from a working population) have been analysed to identify persons with intermediate deficiency, and to compare their respiratory status to control groups with the normal MM type selected from the same population; in some studies, matched-pairs were used [5,8,9,[15][16][17][18][19][20][21][22][23]. Other cross-sectional studies have addressed the question of whether the prevalence of heterozygotes among patients with emphysema or related disease is higher than among control populations [6,7,19,22,[24][25][26][27][28][29].…”

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confidence: 99%

“…These results suggest either that: 1) PiMZ is not a risk factor for the development of lung emphysema [5, 9, 15-17, 19, 21, 24, 25, 30, 35]; or that 2) PiMZ individuals are at increased risk [6,7,10,18,22,23,26,27,29,31,33,36]; or that 3) in addition, cigarette smoking may be an important co-determinant for the development of early onset pulmonary emphysema [20,32,37].…”

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Longitudinal lung function study in heterozygous PiMZ phenotype subjects

et al. 1994

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L Lo on ng gi it tu ud di in na al l l lu un ng g f fu un nc ct ti io on n s st tu ud dy y i in n h he et te er ro oz zy yg go ou us s P Pi iM MZ Z p ph he en no ot ty yp pe e s su ub bj je ec ct ts s Total lung capacity and residual volume increased, whereas forced expiratory volume in one second, expiratory flows, diffusing capacity of the lungs for carbon monoxide, and static transpulmonary pressures decreased in the PiMZ patients. The majority of the controlled functional parameters were found to deteriorate significantly in PiMZ patients during the 10 year period. Trypsin inhibitory capacity in the PiMZ group (mean±SD) was 0.65±0.17 mg·ml -1 as compared to 1.52±0.3 mg·ml -1 in the PiMM group. These changes exceeded the values expected as physiological changes due to ageing.The findings in the present longitudinal study -especially the decrease in elasticity, which is the primary pathophysiological damage in alpha 1 -antitrypsin deficiency -support the concept that the PiMZ phenotype is a risk factor for the development of pulmonary emphysema at younger age than in those without the deficiency.

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Section: Discussionmentioning

confidence: 99%

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Longitudinal lung function study in heterozygous PiMZ phenotype subjects

et al. 1994

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“…However, both of these studies used relatives in the MZ study population and, therefore, the results may not be due to mutations in the α 1 -AT gene. TATTERSALL et al [59] found evidence for greater loss of elastic recoil in MZ versus MM smokers, but estimates of airway function were similar in both groups. HALL et al [60] found that MZ heterozygotes had significantly lower expiratory flow rates, even in the absence of smoking.…”

Section: Alpha 1 -Antitrypsinmentioning

confidence: 96%

Genetic risk factors for chronic obstructive pulmonary disease

Sandford¹,

Weir²,

Paré³

1997

Eur Respir J

193

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Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only a minority of cigarette smokers develop symptomatic disease. Studies of families and twins suggest that genetic factors also contribute to the development of COPD. We present a detailed literature review of the genes which have been investigated as potential risk factors for this disease.The only established genetic risk factor for COPD is homozygosity for the Z allele of the α 1 -antitrypsin gene. Heterozygotes for the Z allele may also be at increased risk. Other mutations affecting the structure of α 1 -antitrypsin or the regulation of gene expression have been identified as risk factors.Genes, including those for α 1 -antichymotrypsin, α 2 -macroglobulin, vitamin Dbinding protein and blood group antigens, have also been associated with the development of COPD. Variants of the cystic fibrosis transmembrane regulator gene have been identified as risk factors for disseminated bronchiectasis.The genetic basis to chronic obstructive pulmonary disease has begun to be elucidated and it is likely that several genes will be implicated in the pathogenesis of this disease. The knowledge gained from such studies may also prove relevant to other inflammatory diseases. Eur Respir J 1997; 10: 1380-1391. REVIEWChronic obstructive pulmonary disease (COPD) is characterized by decreased expiratory flow rates, increased pulmonary resistance and hyperinflation. The most important risk factor for the development of COPD is cigarette smoking [1]. Cigarette smoke, in combination with other factors, leads to two pathophysiological processes in the lung. The first is proteolytic destruction of the lung parenchyma, which increases the size of the airspaces; these eventually coalesce to form emphysematous spaces. The development of emphysema is associated with a loss of lung elastic recoil. The second process is inflammatory narrowing of peripheral airways, which is characterized by oedema, mucus hypersecretion and fibrosis, scarring, distortion and obliteration of peripheral airways. The loss of lung elastic recoil and the narrowing of the peripheral airways combine to decrease maximal expiratory flow from the lung and contribute to hyperinflation. In conjunction with gas exchange abnormalities, hyperinflation produces the symptoms of COPD.Despite the clear association of smoking and airway obstruction, there remains marked interindividual variation in the response to cigarette smoke. This indicates that there are additional genetic or environmental cofactors, which contribute to the development of COPD. It has been estimated that only 10-20% of chronic heavy smokers will ever develop symptomatic COPD [2,3]. Co-factors, such as childhood viral respiratory infections and environmental and occupational pollution, undoubtedly play a role in determining this susceptible subset. Furthermore, there is evidence that genetic susceptibility is of major importance. The epidemiological and clinical data that demonstrate a heredit...

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“…These studies, however, are not without limitations and it has been proposed that Pi-MZ patients self-select away from exposures that would result in impaired pulmonary physiology (156). Other studies have revealed subtle abnormalities of pulmonary function in association with the Pi-MZ genotype, including alterations in pressure/volume curves (157).…”

Section: Definition and Pathophysiology Of Copdmentioning

confidence: 99%