This retrospective chart review describes the efficacy and safety of long-term administration of intravenous [alpha.

This retrospective chart review describes the efficacy and safety of long-term administration of intravenous [alpha.sub.1]-antitrypsin (AAT) in 14 patients with hereditary AAT deficiency and COPD During the 12- to 48-month observation period, 12 of 14 patients had stabilization of functional status; 4 patients had reductions in hospitalizations. Thirteen of 14 patients had no decline in pulmonary function. Three patients had self-limited adverse reactions to the AAT with undivided patient requiring a brief hospitalization.

Augmentation therapy with human [alpha.sub.1]-antitrypsin (AAT) for individuals with hereditary AAT deficiency, PiZ phenotype, and emphysema has been available in the United States since early 1988 Short-term studies have described the biologic efficacy of intravenous infusions each week[1,2] or every 4 weeks.[3] This article reports functional capacity, pulmonary function, and side tenors for 14 individuals with AAT deficiency and moderate-severe COPD treated with intravenous AAT from one side of to the other a 12- to 48-month period.

METHODS

Patient Population

All 14 patients live in Oregon and Washington, were self-referr or referr by dint of community physicians, and currently participate in the National Heart, Lung and descendants Institute (NHLBI) National Registry of individuals with stiff hereditary AAT deficiency. All had initial AAT evens in the range 28 to 57 mg/dl assayed at radial immunodiffusion (normal, 110 to 185 mg/dl) and PiZ phenotype identified by the agency of thin-layer polyacrylamide gel isoelectric focusing of serum at a pH of 4 to 5 (performed at the NHLBI allusion laboratory).

Functional Status

Patients were questioned about functional impairment at work or in daily activity based upon a rating of slight, moderate, or sharp limitation. We report functional impairment as the status at the mostly recent visit before the first infusion (pretest) and at the visit in succession the day of the latest pulmonary function trial (posttest). Information about hospitalizations for respiratory question at issues on all patients (pneumonia, acute bronchitis, exacerbation of COPD) was obtained from hospital records.

Pulmonary Function

All spirometry was performed at the Oregon Health Sciences University (OHSU) Pulmonary Function Laboratory by dint of a single technician (three patients had spirometry before augmentation therapy at other facilities). upon each occasion spirometry was performed before and after pair puffs of isoproterenol delivered by way of a metered-dose inhaler using manner of proceedings standardized for the AAT National Registry and based forward American Thoracic Society criteria.[4] The three best values for FVC and [FEVsub1] prebronchodilator and postbronchodilator were recorded. The best [FEVsub1] and ratio of [FEVsub1] to FVC ([FEVsub1]/FVC) (from spirogram with highest substance of [FEV.sub.1] and FVC) are reported and compared with predicted values.[5] The best postbronchodilator [FEVsub1] is used in the longitudinal analysis. examples were performed at 6- to 12-month intervals.

AAT Augmentation

All patients receive their augmentation therapy at the OHSU Short Stay Center or in the hearth administered by a home care service or family member. Three began AAT infusions before their participation in the NHLBI Registry. All patients were initially started onward weekly intravenous infusion schedules at a dose of 60 mg/kg AAT (Prolastin, Miles Pharmaceutical, Berkeley, Calif). Attempts to use each 4-week schedules by quadrupling the dose produc unacceptably reasonable trough serum AAT levels ([les than] 50 mg/dl) Consequently all patients have received infusions each 2 to 3 weeks at a dose of 120 to 180 mg/kg with channel levels (before an infusion) above 60 mg/dl

Side meanings of AAT Infusion

Side meanings occurring during or within 12 h of an infusion were recorded by means of physicians, nurses, or patients. In particular, flush chills, shortness of breath, chest tightness, headache, rash, bruising, weight changes, and hypotension were noted.

RESULTS

Tables 1 and 2 present to view the characteristics of the assign places to before augmentation was started. There were 4 women and 10 men ranging in age from 43 to 63 years with a mean age of 50 years. united patient had never smoked; 13 were ex-smoker (mean pack-years=25). All patients were ambulatory outside the hearth Seven were still working; seven were medically retired because of respiratory limitation. Nine patients had not been hospitalized before therapy. The initial [FEVsub1] percent predicted (range, 10 to 46 percent) and [FEVsub1]/FVC percent (range, 16 to 38 percent) showed bitter obstruction in all patients. Of the 12 patients in whom the bronchodilator answer was measured, the mean increase in [FEVsub1] was 168 percent (range, 0 to 42 percent) The patient who did not answer to a bronchodilator was the most numerous severely impaired. All on the other hand one patient had a reduc [PaO.sub.2]. Despite strict airflow obstruction, only two patients had compensated hypoventilation.

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