Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation

Abstract

Rationale: Patients with cystic fibrosis periodically experience pulmonary exacerbations. Previous studies have noted that some patients' lung function (FEV(1)) does not improve with treatment.

Objectives: To determine the proportion of patients treated for a pulmonary exacerbation that does not recover to spirometric baseline, and to identify factors associated with the failure to recover to spirometric baseline.

Methods: Cohort study using the Cystic Fibrosis Foundation Patient Registry from 2003-2006. We randomly selected one pulmonary exacerbation treated with intravenous antibiotics per patient and compared the best FEV(1) in the 3 months after treatment with the best FEV(1) in the 6 months before treatment. Recovery to baseline was defined as any FEV(1) in the 3 months after treatment that was greater than or equal to 90% of the baseline FEV(1). Multivariable logistic regression was used to estimate associations with the failure to recover to baseline FEV(1).

Measurements and main results: Of 8,479 pulmonary exacerbations, 25% failed to recover to baseline FEV(1). A higher risk of failing to recover to baseline was associated with female sex; pancreatic insufficiency; being undernourished; Medicaid insurance; persistent infection with Pseudomonas aeruginosa, Burkholderia cepacia complex, or methicillin-resistant Staphylococcus aureus; allergic bronchopulmonary aspergillosis; a longer time since baseline spirometric assessment; and a larger drop in FEV(1) from baseline to treatment initiation.

Conclusions: For a randomly selected pulmonary exacerbation, 25% of patients' pulmonary function did not recover to baseline after treatment with intravenous antibiotics. We identified factors associated with the failure to recover to baseline, allowing clinicians to identify patients who may benefit from closer monitoring and more aggressive treatment.

Figure 1.

Diagram of study cohort.

Figure 2.

FEV₁ for nonresponders and responders at baseline, treatment initiation, and the best FEV₁ in the 3 months after treatment (n = 4,391). Responders are in white, nonresponders are in gray. The boxes represent the middle 50% of patients; the whiskers include all patients in each group. The horizontal line within the box represents the median FEV₁. The x axis represents three time points: the best FEV₁ in the 6 months before admission (baseline); FEV₁ at treatment initiation (exacerbation); and the best FEV₁ in the 3 months after treatment (follow-up).

Figure 3.

Final model for the failure to recover to baseline FEV₁. The first column lists the variables included in the model. The next column is the estimated odds ratio (OR) and 95% confidence intervals (CI) for the variable. An OR greater than 1 indicates an association with a higher risk of failing to recover to baseline. The next three columns give the estimated OR and 95% CI. A normal BMI is defined as greater than or equal to 18.5 kg/m² for adults or greater than or equal to 5th percentile for children. ABPA = allergic bronchopulmonary aspergillosis; BMI = body mass index; CF = cystic fibrosis; MRSA = methicillin-resistant Staphylococcus aureus.