Israel Medical Association Journal

Abstract

Background: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

 

Idiopathic pulmonary arterial hypertension (IPAH) is an isolated small-vessel disease comprising vasoconstriction, remodeling and thrombosis of small pulmonary arteries. However, there is evidence that IPAH[1] does not respect anatomic boundaries and might extend into large vessels such as large central thrombi. On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH) represents a distinct category of pulmonary hypertension as it is thought to be due to an occlusion of the major pulmonary arteries following a thromboembolic event. However, it is currently evident that in most patients, there is a concomitant small-vessel disease. The involvement of both small and large vessels in both IPAH and CTEPH[2] together with a high incidence of silent thromboembolic events might create difficulties in identifying the true cause of pulmonary hypertension. An accurate diagnosis of the cause determines the management and prognosis. Patients with CTEPH can potentially be offered curative surgery in the form of pulmonary endarterectomy; however, oxygen, vasodilators, anticoagulation, and lung transplantation are more feasible options for IPAH.

Background: Unexplained pulmonary hypertension is assumed to occur mainly in young adults.

Objectives: To describe the features of the disease in older patients and compare them to those in PHT[1] patients of all ages.

Methods: We conducted a retrospective evaluation of the files of patients over 65 years of age in whom UPHT[2] was diagnosed between 1987 and 1999 at two PHT centers serving a population of 4 million. Patients were followed for survival until March 2003. Clinical variables of the study patients were compared to those in PHT patients of all ages.

Results: The study group included 14 patients, 10 females and four males, with a mean age of 70.5 ± 6.7 years. The calculated mean annual incidence of UPHT for the study population was one new case per year per million persons. Seven patients (50%) had systemic hypertension. The mean interval from onset of symptoms to diagnosis was 8.3 months. At diagnosis, 64% of patients had functional capacity of III-IV according to the New York Heart Association classification, and 43% had right heart failure. Mean systolic pulmonary artery pressure was 80 ± 21 mmHg, peripheral vascular resistance 11.7 ± 7 mmHg/L/min, cardiac index 2.16 ± 0.81, and mean right atrial pressure 10.5 ± 5.9 mmHg. Median survival time was 43 months; survival rates for 1 year, 3 years and 5 years were 92.6%, 50%, 40%, respectively. Compared to data from the U.S. National Institute of Health Registry, UPHT in older patients is more common in females, but the incidence as well as clinical, hemodynamic and survival parameters are similar to those in PHT patients at any age.

Conclusions: UPHT occurs in the elderly more frequently than previously thought, with similar features in PHT patients of all ages. The coexistence of systemic and pulmonary hypertension warrants further investigation.

Background: Data regarding the epidemiology of secondary pulmonary hypertension are scanty.

Objectives: To describe the spectrum and relative incidence of background diseases in patients with significant secondary PHT.

Methods: We identified 671 patients with systolic pulmonary artery pressure of 45 mm Hg or more from the database of the echocardiographic laboratory. Their background diseases were recorded and classified into three subgroups: cardiac, pulmonary and pulmonary vascular disease without pulmonary parenchymal disease. Age at the first echocardiographic study, gender and systolic PAP values were recorded. Data between the three subgroups were compared.

Results: The mean age of the patients was 6515 years, mean systolic PAP 6114 mm Hg and female:male ratio 1.21:1. At the time of diagnosis 85% of the patients were older than 50. PHT was secondary to cardiac disease in 579 patients (86.3%), to PVD without PPD in 54 patients (8%) and to PPD in only 38 patients (5.7%). Mean age and mean systolic PAP did not differ significantly among the three subgroups. There was a significantly higher female: male ratio in patients with PVD without PPD compared with cardiac or pulmonary diseases (1.7:1 vs. 1.2:1 and 1.7 vs. 0.8:1 respectively, P0.05).

Conclusions: The majority of patients with significant PHT are elderly with heart disease. PVD without PPD and chronic PPD are a relatively uncommon cause of significant PHT. Since the diagnosis of PHT is of clinical significance and sometimes merits different therapeutic interventions, we recommend screening by Doppler echocardiography for patients with high risk background diseases.