Use of FEF25-75% to Guide IgG Dosing to Protect Pulmonary Function in CVID

Abstract

Immunoglobulin replacement therapy (IGRT) can protect against lung function decline in CVID. We tested whether increasing IgG dosage was beneficial in patients who exhibited a decline in forced expiratory flow at 25-75% (FEF25-75%) even though they were receiving IgG doses within the therapeutic range. Of 189 CVID patients seen over 12 years, 38 patients met inclusion criteria, were seen on ≥ 3 visits, and demonstrated a ≥ 10% decrease in FEF25-75% from visits 1 to 2. FEF25-75%, forced expiratory flow at 1 s (FEV1), and FEV1/FVC at visit 3 were compared among those with non-dose adjustment (non-DA) versus additional IgG dose adjustment (DA). Three FEF25-75% tiers were identified: top (> 80% predicted), middle (50-80%), and bottom (< 50%). DA and non-DA groups did not differ in clinical infections or bronchodilator use, although the non-DA group tended to use more antibiotics. In the top, normal tier, FEF25-75% increased in DA, but the change did not achieve statistical significance. In the middle moderate obstruction tier, visit 3 FEF25-75% increased among DA but not non-DA sets (11.8 ± 12.4%, p = 0.003 vs. 0.3 ± 9.9%, p = 0.94). Improvement in FEV1/FVC at visit 3 was also significant among DA vs. non-DA (7.2 ± 12.4%, p = 0.04 vs. - 0.2 ± 2.7%, p = 0.85). In the bottom, severe tier, FEF25-75% was unchanged in DA (- 0.5 ± 5.2%, p = 0.79), but increased in non-DA (5.1 ± 5.2%, p = 0.02). Among IGRT CVID patients with moderate but not severe obstruction as assessed by spirometry, increasing IgG dosage led to an increase in FEF25-75% and FEV1/FVC.

Keywords: Common variable immunodeficiency (CVID); FEF25–75%; IgG dose adjustment; Immunoglobulin replacement therapy; Prophylactic antibiotics; Spirometry.

Fig. 1.

FEF25–75% at visits 1, 2, and 3 for the non-Dose Adjustment (non-DA) and the Dose Adjustment three visit sets (DA). Top tier: dotted line. Middle tier: solid line. Bottom tier: dotted-dashed line.

Fig. 2.

For changes in FEF25–75%, the Dose Adjustment sets in the middle tier section showed a statistically significant increase in FEF25–75% after dose increase; whereas the non- Dose Adjustment sets did not. The FEF25–75% at visits 2 and 3 are shown. The solid dashed line indicates the mean line with the 95% confidence interval shown in gray.

Fig. 3.

For changes in FEV1/FVC, the Dose Adjustment sets in the middle tier section showed a statistically significant increase in FEV1/FVC after dose increase; whereas the non-Dose Adjustment sets did not. The FEV1/FVC at visits 2 and 3 are shown. The solid dashed line indicates the mean line with the 95% confidence interval shown in gray.

Fig. 4.

Changes in spirometric values in percent of predicted from visit 2 to visit 3 as a function of the absolute increase in IGRT therapy in grams per four week intervals. As the absolute dose increases, there is trend for an increase in the FEF25–75% only in the top tier group. In the middle group, there was an increase in FEF25–75% and FEV1/FVC in almost all of the study subjects receiving at least a 5 gram increase in dosage per 4 week period, although there was no obvious benefit to receiving more than 5 grams. X axis: Absolute change in dose per four weeks in grams. Y axis: Change in percent of (A) FEF25–75%, (B) %FEV1, (C) %FVC and (D) FEV1/FVC. Solid dots represent non-Dose Adjustment, x represents Dose-Adjustment group.