Alpha1-Antitrypsin Deficiency in COPD: Clinical Implications

, College of Physicians and Surgeons, Columbia University, NY

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Which Asthmatics Should be Screened for Alpha1-Antitrypsin Deficiency?

As discussed previously, the presence of wheeze and a bronchodilator response on lung function testing is common in patients with COPD. Methacholine challenge studies show a high prevalence of bronchial reactivity and cannot be used to distinguish COPD from asthma with confidence.[27] These patients may also show an elevated IgE and atopy. Furthermore, the young age of patients with alpha1-AT would tend to bias the diagnosis toward asthma rather than a potentially more serious condition.[34] Data from the NHLBI Registry indicate that 35% of patients self-report (ie, have been given) the diagnosis of asthma and 29% report allergies affecting the respiratory tract.

Given the difficulty of diagnosing emphysema in the presence of asthma, the following factors should alert the clinician to the possibility of underlying hereditary emphysema in a patient diagnosed with asthma:

  • A family history of lung disease or childhood liver disease,

  • A complaint of dyspnea, usually progressive over years, not related to attacks of wheezing. In alpha1-ATD early development of emphysema is invariably associated with current or prior cigarette smoking,

  • In the patient below age 60, serial lung function studies performed in a well-run laboratory that show the presence of an obstructive pattern; the obstructive pattern may be partially but not totally reversed by bronchodilator. The flow volume loop may show dynamic airway collapse (Fig. 5). This same pattern may occur however in chronic asthma as a result of airway remodeling,

Typical clinical findings for a 49-year-old man with severe alpha 1-ATD-related emphysema and bronchial asthma. Note the dynamic airway collapse represented by the rapid fall in flow with continuing expiration (inset box), the near normal FVC, the improvement in FVC and FEV 1 following bronchodilator aerosol, and the normal inspiratory loop. The forced expiratory time is remarkably prolonged at 14 seconds.
  • No demonstration of a bronchodilator response after repeated lung function testing and a rapid fall in FEV1 (greater or equal to 50 cc/year) over a sustained period of time may indicate the development of fixed airway obstruction. To detect these subtle changes, such studies should be performed in a pulmonary function laboratory with sufficient quality control to ensure a high degree of reproducibility,

  • A reduced diffusion capacity (<80% predicted) and coefficient may raise the possibility of emphysema. These findings are however nonspecific and do not provide greater sensitivity in the absence of airway obstruction (unpublished observations, NHLBI Registry). Yet such a reduction would be unusual in the simple asthmatic,

  • A chest radiograph showing persistent hyperinflation or hyperlucency (Fig. 2) in the absence of an acute asthmatic attack. Occasional patients show evidence on chest radiograph of bronchiectasis, and

  • Finally a high resolution CT scan, in those with an unremarkable chest radiograph, may show basilar emphysema that is atypical for the asthmatic patient or smoker (where emphysema tends to occur at the lung apices). The diagnosis would be confirmed with a serum alpha1-AT level less than 11 mcM (approximately 80 mg/dL).

In summary there are two ways to diagnose alpha1-ATD in a patient who wheezes: screen all asthmatics of appropriate age and race, or, maintain a constant high level of suspicion.

Screening for Alpha1-ATD. The most relevant screening test for those in whom alpha1-ATD is suspected, would be a serum alpha1 AT level sent to a reputable laboratory. Although acute inflammatory conditions may influence the result, they do not raise the concentration to normal levels in those who are deficient.

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