Determinants of exhaled breath condensate pH in a large population with asthma

Abstract

Background: Exhaled breath condensate (EBC) pH is 2 log orders below normal during acute asthma exacerbations and returns to normal with antiinflammatory therapy. However, the determinants of EBC pH, particularly in stable asthma, are poorly understood. We hypothesized that patients with severe asthma would have low EBC pH and that there would be an asthma subpopulation of patients with characteristically low values.

Methods: We studied the association of EBC pH with clinical characteristics in 572 stable subjects enrolled in the Severe Asthma Research Program. These included 250 subjects with severe asthma, 291 with nonsevere asthma, and 31 healthy control subjects.

Results: Overall, EBC in this population of stable, treated study subjects was not lower in severe asthma (8.02; interquartile range [IQR], 7.61-8.41) or nonsevere asthma (7.90; IQR, 7.52-8.20) than in control subjects (7.9; IQR, 7.40-8.20). However, in subjects with asthma the data clustered below and above pH 6.5. Subjects in the subpopulation with pH < 6.5 had lower fraction of exhaled NO (FeNO) values (FeNO = 22.6 ± 18.1 parts per billion) than those with pH ≥ 6.5 (39.9 ± 40.2 parts per billion; P < .0001). By multiple linear regression, low EBC pH was associated with high BMI, high BAL neutrophil counts, low prebronchodilator FEV(1) ratio, high allergy symptoms, race other than white, and gastroesophageal reflux symptoms.

Conclusion: Asthma is a complex syndrome. Subjects who are not experiencing an exacerbation but have low EBC pH appear to be a unique subpopulation.

Figure 1.

Exhaled breath condensate pH population distribution in normal control subjects (green line), subjects with stable mild to moderate asthma (blue dashed line), and subjects with stable severe asthma (red dotted line). Note the distribution of some subjects with subjects substantially below pH 6.5. Individual subjects are shown as hash marks on the x-axis.

Figure 2.

The relation between pH and phenotypic features. A, BMI. B, Fraction of BAL neutrophils. C, FEV₁. D, GER symptoms. Asthma severity is denoted by the following: green dot, control; blue X, not severe; red circle, severe. Note that there is a natural distribution of these data above and below pH 6.5. GER = gastroesophageal reflux.

Figure 3.

The relationship between pH and allergy symptoms in spring and winter. Asthma severity is denoted by symbols: red dot, normal; blue X, not severe; green circle, severe.

Figure 4.

The relationship between pH and response to GERD symptoms by questionnaire (yes/no). Asthma severity is denoted by symbols: red, normal; blue, not severe; green, severe. GERD = gastroesophageal reflux disease.