Alpha1-Antitrypsin Deficiency in COPD: Clinical Implications

, College of Physicians and Surgeons, Columbia University, NY

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In This Article

Treatment of Asthma in the Setting of Alpha1-ATD

Alpha1-AT augmentation therapy. The role of alpha1-AT replacement (Prolastin®)[8] in ameliorating bronchial hyperreactivity has not been established. Initial experiments with recombinant IV alpha1-AT have shown a failure to maintain adequate long-term serum levels due to increased urinary excretion, possibly as a result of a lack of carbohydrate side chains.

Unpublished data from the NHLBI Registry indicate that IV replacement therapy is effective in diminishing the progressive fall in FEV1 by at least 25% in those with baseline FEV1 readings of between 35% to 49% predicted. There is no evidence to indicate that replacement therapy would be less effective in those with asthma. In addition, 29 normal subjects who underwent bronchoalveolar lavage after administration of 200 mg human alpha1-AT (Prolastin®) by nebulizer showed alveolar concentrations double baseline for at least 36 hours, with no associated side effects noted.[40] Bronchoalveolar lavage cell counts also remained unaffected by aerosolized alpha1-AT, raising an intriguing possibility that therapy with inhaled alpha1-AT may ameliorate bronchial hyperreactivity in some subjects. However, deposition of aerosol in those with emphysema is likely to be less homogenous.

Potential benefits of gene therapy. Although there have been no reports, the use of a human plasma-derived concentrate for the replacement of alpha1-AT has potential for transmission of infections such as viral hepatitis and Creutzfeldt Jakob disease. Production of transgenic material from specially bred animals or insertion of the normal gene into human cells using retroviral or adenoviral vectors, would clearly be advantageous, but as yet, have not been fully realized.

Pharmacologic approach. Treatment of asthma in the presence of alpha1-ATD includes therapy with bronchodilators and inhaled steroids. The latter are important to reduce airway inflammation in a population that may be susceptible to the long-term effects of bronchial hyperreactivity. In addition, several of my patients have described amelioration of symptoms of dyspnea and wheezing with leukotriene inhibitors and Prolastin itself. Even if asthma is present, I do not maintain my patients with alpha1-ATD on systemic steroid therapy given the long-term adverse effects of such treatment, particularly on respiratory muscle function. Steroids would be given during acute exacerbations and tapered rapidly thereafter. And finally, supportive therapy for the patient and family are critical in the management of alpha1-ATD.

Preventive measures. It is imperative that those individuals who have not stopped smoking, do. They should be informed that if they fail to do so, they will develop emphysema and that premature death will occur. Several products to aid in quitting are now on the market and others will soon be available.

Patients with alpha1-ATD should be evaluated for allergy desensitization therapy.[41,42] In a recently reported study, atopy was present in 50% of patients.[24] Indoor antigens from cats, cockroaches, dust mites and molds are powerful sensitizers and allergy to these inhaled antigens may increase bronchial reactivity in such subjects. Appropriate steps should be made to reduce the level of environmental antigen if the patient has asthma and is found to be sensitive.

All patients should receive a yearly prophylactic influenza immunization and antibiotics should be started at the first sign of bronchitis or a lower respiratory infection.

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