CHEST
Volume 119, Issue 3, March 2001, Pages 737-744
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Clinical Investigations
Longitudinal Follow-up of Patients With α1-Protease Inhibitor Deficiency Before and During Therapy With IV α1-Protease Inhibitor

https://doi.org/10.1378/chest.119.3.737Get rights and content

Background:

The efficacy of IV augmentation therapywith human α1-protease inhibitor (α1-Pi) inpatients with severe α1-Pi deficiency is still underdebate.

Study objectives:

To evaluate the progressionof emphysema in patients with α1-Pi deficiency before and during a period in which they received treatment withα1-Pi.

Design:

Multicenter, retrospective cohort study.

Settings:

Outpatientclinics of 26 university clinics and pulmonary hospitals.

Patients:

Ninety-six patients with severeα1-Pi deficiency receiving weekly augmentation therapywith human α1-Pi, 60 mg/kg of body weight, had a minimumof two lung function measurements before and two lung functionmeasurements after augmentation therapy was started. Lung function datawere followed up for a minimum of 12 months both before and duringtreatment (mean, 47.5 months and 50.2 months, respectively).

Measurements and results

Patients were grouped accordingto the severity of their lung function impairment. The change inFEV1 was compared during nontreatment and treatmentperiods. In the whole group, the decline in FEV1 wassignificantly lower during the treatment period (49.2 mL/yr vs 34.2mL/yr, p = 0.019). In patients with FEV1 > 65%, IVα1-Pi treatment reduced the decline in FEV1by 73.6 mL/yr (p = 0.045). Seven individuals had a rapid decline of FEV1 before treatment, and the loss in FEV1could be reduced from 256 mL/yr to 53 mL/yr (p = 0.001).

Conclusion:

Some patients with severe α1-Pideficiency and well-preserved lung function show a rapid decline inFEV1. These patients profit from weekly IV therapy with human α1-Pi and have less rapid decline if treated. Earlydetection of patients at risk and early start of augmentation therapymay prevent accelerated loss of lung tissue.

Section snippets

Materials and Methods

For this cohort study, we used one database that contained lungdata before the institution of α1-Pi therapyand a second database of a phase IV drug surveillance study.

Results

A total of 96 patients (62 males and 34 females, p = 0.004) wereavailable for analysis. The mean time of observation was 47.5 ± 28.1months (range, 12.2 to 148.3 months) before augmentation therapy and50.2 ± 30.2 months (range, 12 to 148.6 months) during the treatmentperiod. The mean total observation time was 98.9 ± 36.6 months(range, 24.9 to 196.3 months). Twenty-eight patients had an observationperiod > 10 years.

The majority of patients had PiZ phenotypes, and the frequencies of thephenotypes

Discussion

This study is the first intraindividual studycomparing lung function decline in 96 patients withα1-Pi deficiency before they receivedaugmentation therapy to a period of time in which they received weeklyIV augmentation therapy. There was a significantly lower decline inFEV1 during the period patients received IVaugmentation therapy compared to the period with out specific treatment. The overall reduction of the decline in FEV1 from49.2 to 34.3 mL/yr by 15 mL/yr is similar to the reduction

Additional Participants of the WATL Group for α1-PiDeficiency

R. Loddenkemper, N. Schönfeld, Berlin; E. Kaukel, R.D. Staud, Hamburg; G. Kanzow, Großhansdorf; K.J. Wiemann, Bad Schwartau; J. Braun, Lübeck; U. Lepp, Borstel; N. de Wall, Sande; K. Eberhardt, Bremen; H. Fabel, Hannover; G. Goeckenjan, Immenhausen; R. Kappes, Duesseldorf; E.W. Schmidt, Bochum; H. Steveling, Essen; J. Lorenz, J. Schlegel, W. Schmidt, Mainz; R. Buhl, J. Bargon, Frankfurt;V. Schulz, Heidelberg; R. Dierkesmann, Gerlingen; J.C. Virchow Jr.,Freiburg; M. Schwaiblmair, R.W. Hauck,

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    Dr. Wencker was supported in part by Bayer Corporation, by aneducational grant given in conjunction with a clinical trial of inhaledα1-protease inhibitor and not related to this analysis.

    Dr. Banik was employed by Bayer Vital as astatistician.

    Significant portions of this article are part of a doctoral thesis byDr. Fuhrmann.

    A complete list of participants is located in the Appendix.

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