Docosatetraenoyl LPA is Elevated in Exhaled Breath Condensate in Idiopathic Pulmonary Fibrosis

Sydney B Montesi; Susan K Mathai; Laura N Brenner; Irina A Gorshkova; Evgeny V Berdyshev; Andrew M Tager; Barry S Shea


BMC Pulm Med. 2014;14(5) 

In This Article


Patient Characteristics

Relevant demographic and clinical data for IPF subjects (n = 11) and controls without lung disease (n = 11) on whom EBC and plasma LPA measurements were performed are summarized in Table 1. Of the 11 IPF subjects, 6 were diagnosed by surgical lung biopsy, and 5 were diagnosed by clinical and radiographic criteria alone. The mean age was 67.7 (+/− 8.5) years in the IPF group and 68.2 (+/− 7.1) years in the control group. The male to female ratio was 10:1 in the IPF group and 9:2 in the control group. There were no current smokers in either group; however, both groups contained former smokers. Spirometry data were available on 8/11 subjects and DLCO (diffusion capacity of carbon monoxide) data on 7/11 IPF subjects as shown in Table 1. Spirometry was not obtained on control subjects. Of the available pulmonary function results, the majority of testing (5/8) was performed on the day of EBC and plasma collection. All pulmonary function testing was performed within 15 days of sample collection. Supplemental oxygen was needed for 7/11 of IPF subjects. None of the IPF subjects were taking inhaled corticosteroids at the time of data collection.

Levels of LPA in Exhaled Breath Condensate and Plasma

Nine different LPA species were detected in the EBC from IPF subjects and controls (Table 2). Of these, docosatetraenoyl (22:4) LPA exhibited a statistically significant difference between the two groups, with levels being significantly higher in IPF patients compared to controls (9.18 vs. 0.34 pM; p = 0.001). Furthermore, there was minimal overlap between EBC 22:4 LPA levels in IPF patients and controls. It was detected at levels > 1.5 pM in 9/11 IPF patients but was undetectable in all but three of the controls, and in only one control was the level > 0.4 pM (Figure 1). For the remaining eight LPA species, no statistically significant differences were detected between the two groups; however, there were trends towards increased levels of 18:2 LPA and 20:3 LPA in EBC of IPF patients (p = 0.13 and p = 0.055, respectively). There was no significant difference in the total amount of LPA in EBC between the two groups (664.69 +/− 83.03 vs. 766.15 +/− 137.35 pM, p = 0.73). Thirteen different LPA species were detected in plasma from IPF subjects and controls (Table 3). None of these 13 species showed statistically significant differences between the two groups, nor was there a statistically significant difference in the total amount of LPA between the two groups (mean control LPA 77.90 +/− 22.31 nM and mean IPF 64.51 +/− 12.82 nM, p = 0.10).

Figure 1.

Exhaled breath condensate (EBC) LPA levels. Levels of docosatetraenoyl (22:4) LPA (A) and total LPA (B) in the exhaled breath condensate (EBC) of IPF patients and controls, as determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Levels of 22:4 LPA, but not total LPA, were significantly higher in IPF patients vs. controls, with minimal overlap in EBC 22:4 LPA levels between the two groups. *p = 0.001 for the comparison of IPF vs. controls by Mann Whitney test.

Docosatetraenoyl (22:4) LPA and Subject Characteristics

The average EBC 22:4 LPA level in IPF patients was 9.18 +/− 5.19 pM. There was no correlation between 22:4 LPA levels and disease severity, as determined by percent predicted FVC or DLCO (data not shown). One subject had an EBC 22:4 LPA level of 60 pM, which far exceeded the standard deviation of the mean. This subject was a 46 year-old man with biopsy-proven usual interstitial pneumonia (UIP) who required hospital admission for worsening respiratory status in the setting of a suspected IPF exacerbation. Spirometry performed during the patient's hospitalization and within 10 days of EBC collection demonstrated a severe restrictive deficit, with a FVC of 33% predicted. He subsequently developed respiratory failure and eventually underwent lung transplantation within one month of sample collection. Pathologic review of the explanted lung revealed UIP in the accelerated phase. None of the other ten IPF patients in this study were in the midst of IPF exacerbations during sample collection.