MONTREAL, Quebec—Patients with pulmonary arterial hypertension (PAH) due to connective tissue disease (CTD) have worse pulmonary capillary endothelial dysfunction than patients with idiopathic PAH (IPAH), largely because they have less activity of pulmonary capillary endothelium-bound angiotensin-converting enzyme (PCEB-ACE). David Langleben, MD, from Sir Mortimer B. Davis Jewish General Hospital in Montreal, Quebec, Canada, reports the first comparative study of the two types of PAH in Arthritis & Rheumatism.¹

“[T]he results of our study identify etiology-specific patterns of pulmonary capillary endothelial metabolic dysfunction in patients with PAH with a greater degree of dysfunction in patients with PAH-CTD, in whom a combination of reduced PCEB-ACE and [functional capillary surface area] FCSA loss occurs, in contrast to patients with IPAH, who seem to experience only loss of FCSA,” Dr. Langleben said.

Rare comparison of two types of PAH

Dr. Langleben and colleagues set out to study the effects of PAH on PCEB-ACE activity in 19 patients with PAH-CTD and in 25 patients with IPAH. They compared these patients to results in 23 normal controls. The study included single-pass transpulmonary percent metabolism (%M) and hydrolysis of an ACE synthetic substrate, both of which reflect enzyme activity per capillary. They also calculated FCSA, normalized to body surface area.

The analysis showed

• metabolically functional pulmonary capillary bed reduced to an equal extent in PAH-CTD and IPA
• %M and hydrolysis reduced in PAH-CTD but not in IPAH

According to the investigators, ACE activity on the pulmonary capillary endothelial cells is diminished in PAH-CTD but not in IPAH and that pulmonary endothelial metabolic function differs between PAH types.

“This study also provides the first functional evidence that a reduced diffusing capacity for carbon monoxide value in patients with PAH-CTD is related to the degree of FCSA loss,” Dr. Langleben said. The researchers suggest that future studies should explore whether detecting endothelial dysfunction early in the course of PAH could help predict subsequent development of accelerated PAH.

Translating research into practice

“Our techniques should be considered as specific research tools rather than as widely useful clinical or diagnostic assays. They nevertheless provide quantifiable indices of pulmonary endothelial function, display functional differences between PAH etiologic types, and may be applicable to analysis of disease progression and response to therapy,” Dr. Langleben said.

Reference

1. Langleben D, Orfanos SE, Giovinazzo M, et al. Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension. Arthritis Rheum. 2008;58:1156-1164.