Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized, controlled study.

OBJECTIVE: Iloprost is a stable prostacyclin analogue which has been shown to be effective in the short-term symptomatic treatment of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). The aim of this study was to evaluate the effects of long-term cyclic therapy with iloprost in comparison with nifedipine on the skin score, pulmonary function and Raynaud's severity score in patients with SSc and RP. METHODS: We conducted a 12-month prospective, randomised, parallel-group, blind-observer trial to compare the effects of intravenously infused iloprost (2 ng/kg/min on 5 consecutive days over a period of 8 hours/day and subsequently for 8 hours on one day every 6 weeks) with those of conventional vasodilating therapy with nifedipine (40 mg/day for os) in 46 patients with SSc and RP. RESULTS: At 12 months, iloprost but not nifedipine reduced the skin score (iloprost: from 13.26 +/- 2.05 to 9.26 +/- 1.32, p = 0.002; nifedipine: from 10.83 +/- 2.09 to 12.17 +/- 3.02, p = n.s.; iloprost vs nifedipine: p = 0.016) and the RP severity score (iloprost: from 2.17 +/- 0.2 to 1.22 +/- 0.13, p = 0.02 vs baseline; nifedipine: from 2.08 +/- 0.34 to 1.33 +/- 0.22, p = n.s.). Carbon monoxide diffusing capacity (DLCO), expressed as % of the predicted normal value, worsened significantly in the nifedipine group (from 69.6 +/- 7.4% to 61.5 +/- 6.5%, p = 0.044) and remained stable in patients treated with iloprost (from 53.2 +/- 4.8 to 56.0 +/- 4.6%, iloprost vs nifedipine: p = 0.026). CONCLUSION: In SSc patients, cyclic intravenous iloprost infusion is able to control vasospastic disease. Our results suggest that it might also act as a disease-modifying agent, as it seems to improve the course of the disease. Further studies principally focused on organ involvement and the natural history of the disease are needed to confirm our results.

Prognostic value of pulmonary hypertension in patients with chronic interstitial lung disease referred for lung or heart-lung transplantation.

BACKGROUND: The purpose of this study was to identify precise and reliable prognostic parameters in patients affected by serious chronic interstitial lung disease, who were undergoing screening for lung or heart-lung transplantation. METHODS: Hemodynamic and respiratory function parameters of 67 patients (43 with idiopathic pulmonary fibrosis, 18 with histiocytosis X, and 6 with lymphangioleiomyomatosis) undergoing clinical screening for lung transplantation. RESULTS: Statistical analysis showed that hemodynamic and respiratory function parameters in patients affected by histiocytosis X and idiopathic pulmonary fibrosis were not related to survival time. Moreover, the degree of pulmonary hypertension showed no correlation between respiratory function parameters in all the groups of diseases examined. Patients affected with histiocytosis X, even with higher degrees of pulmonary hypertension, had a better survival rate (p < 0.0005) compared with patients with idiopathic pulmonary fibrosis. CONCLUSIONS: Hemodynamic and respiratory parameters obtained during the clinical screening for lung transplantation do not predict survival and cannot be used as prognostic indicators.

Selection and evaluation of recipients for heart-lung and lung transplantation: the Niguarda Hospital experience.

Between January 1989 and February 1993, 52 patients were evaluated at Niguarda Hospital for lung or heart and lung transplantation. Of the 35 that entered the waiting list, a total of 19 were transplanted (14 at other institutes before our surgical programme became operative, and 5 at our hospital). Recipient selection and evaluation criteria, and timing of transplantation in the different diseases are discussed.

Technical aspects of oxygen saving devices.

Oxygen economizing devices have been extensively studied, both at rest and during muscular exercise, in an attempt to increase the autonomy of a portable oxygen apparatus. The aim of this study is threefold: first, to suggest a simple method to verify in a simple way the technical accuracy of a demand flow oxygen delivery device; second, to suggest how we can monitor in a simple way the clinical efficacy of an economizer; and third, to remember that we can utilize an oxygen saving device to give a better protection than nasal prongs against the worsening of HbO2 desaturation induced by exercise.

A reservoir nasal cannula improves protection given by oxygen during muscular exercise in COPD.

We verified the utility of an oxygen economizer (Pendant Oxymizer) in assuring greater protection than nasal prongs against worsening of oxyhemoglobin resting desaturation (delta SaO2) induced by muscular exercise in 16 patients (ten with chronic obstructive pulmonary disease [COPD] and six with restrictive pulmonary disease). This worsening was quantified as desaturation surface accumulated within five minutes of exercise and was expressed in arbitrary units (au). Each patient carried out the same exercise three times, in a randomized fashion (breathing air or breathing supplemental oxygen [3 L/min] delivered by either nasal prongs or by oxygen economizer). In patients with obstructive disease, delta SaO2 was reduced from 38 +/- 12.0 au when they were breathing air to 18.1 +/- 11.7 au when breathing oxygen by nasal prongs (p less than 0.001) and to 10.1 +/- 9.5 au when breathing oxygen by economizer (p less than 0.001). In patients with restrictive disease, delta SaO2 was reduced from 35.6 +/- 9.9 au when breathing air to 14.9 +/- 10.2 au breathing oxygen by nasal prongs (p less than 0.01) and to 13.7 +/- 10.3 au breathing oxygen by economizer (p less than 0.01). The difference between breathing by economizer and nasal prongs was significant (paired t-test; p less than 0.01) only in patients with COPD. One explanation could lie in the different values of the respiratory rate, which was significantly greater in patients with restrictive disease (20.7 +/- 1.2 breaths per minute at rest and 25.8 +/- 1.5 with exercise) than in patients with obstructive disease (15.3 +/- 1.2 breaths per minute at rest and 20.8 +/- 1.4 with exercise).

Influence of ACE inhibition on pulmonary haemodynamics and function in patients in whom beta-blockers are contraindicated.

The effects of captopril have been studied in 19 patients suffering from chronic obstructive pulmonary disease (COPD). In 9 of these patients with pulmonary hypertension (mean pulmonary artery pressure greater than 20 mm Hg), we studied the effects of the drug on pulmonary haemodynamics, blood gases and systemic circulation. Haemodynamic data were recorded before oral captopril 50 mg and for the next 60 minutes. Following captopril administration, significant reductions in mean pulmonary artery pressure (PAP) (P less than 0.05), in mean pulmonary wedge pressure (PWP) (P less than 0.05) and in total pulmonary resistance (TPR) were noted; significant reductions in mean brachial artery pressure (BAP) and systemic vascular resistance (SVR) were also recorded, while cardiac output, heart rate and blood gas tensions showed no significant changes. Furthermore, the higher the hypoxaemia was, the greater the reduction in BAP (P less than 0.05). In the other 10 COPD patients with moderate essential hypertension, captopril was given as monotherapy (75-10 mg/day) for 60 days. We found no significant modification of the various respiratory function tests except for an increase in the vital capacity (P less than 0.05). Systolic blood pressure and diastolic blood pressure were reduced both in the supine and in the standing position and there were no side effects, in particular no bronchospasm even in the patients responsive to bronchodilator drugs. Our data suggest that captopril is an effective and safe drug when administered to COPD patients with essential hypertension. Moreover, in these patients, it may protect the pulmonary circulation from hypoxic pulmonary vasoconstriction.

Treatment of essential hypertension with captopril in patients with chronic obstructive pulmonary disease.

The effects of captopril have been studied in 10 patients suffering from chronic obstructive pulmonary disease (COPD) with moderate essential hypertension. Captopril was given as monotherapy (75-100 mg/day) over a period of 60 days. The following effects of captopril were seen in these patients: a significant reduction of systolic blood pressure (P less than 0.01) and of diastolic blood pressure (P less than 0.001), both in the supine and in the standing position; a significant increase of the vital capacity (P less than 0.05); no significant change in other various respiratory function tests or of heart rate, and no side effects, including bronchospasm in the patients sensitive to bronchodilator drugs. The present data suggest that in COPD patients with essential hypertension, captopril is an effective hypotensive agent and has no adverse effects in pulmonary function.

A portable oxygen system corrects hypoxemia without significantly increasing metabolic demands.

Some patients with chronic cor pulmonale have hypoxemia only during normal daily activity. This can be corrected by portable oxygen. Whether or not the weight of the apparatus (4.2 kg) adds an additional metabolic demand of sufficient magnitude to cancel or outweigh the advantages of portable oxygen is the subject of this report in 6 patients with chronic obstructive pulmonary disease and 2 with kyphoscoliosis. All received standardized treadmill exercise while breathing room air, and the same exercise with a portable liquid oxygen system sitting on the floor or carried by the patients. The additional load created only a 6.7% increase in CO2 production and did not reverse the supplemental oxygen benefit to arterial oxygen saturation under the experimental conditions of the study.

Value of nocturnal monitoring of transcutaneous O2 and CO2 pressures in adults with respiratory failure.

We have evaluated the reliability of the transcutaneous (t.c.) method of measurement of arterial PO2 and PCO2 in adult man. In 33 simultaneous measurements of 9 normals and 12 patients with a wide range of hypoxemia, we found: t.c. PCO2 = 3.62 + 1.29 PaCO2 +/- 7.3 (r = 0.96) and t.c. PO2 = 11.14 + 0.86 PaO2 +/- 9.89 (r = 0.92). Recalculating t.c. PCO2 to 37 degrees C we can obtain: t.c. PCO2 = 2.7 + 0.97 X PaCO2, stating that there is no significant difference between t.c. PCO2 and PaCO2. The t.c. apparatus detects 10 and 90% O2 pressure changes with a delay of time of about 15 s and 1 min, respectively; the t.c. method is therefore not suitable for detecting changes in PaO2 caused by sleep apnea of short duration. On the contrary the t.c. method provided a useful monitoring of arterial PO2 and PCO2 changes during the night in chronic obstructive pulmonary disease (COPD) and non-COPD patients. A nocturnal monitoring of t.c. PO2 and PCO2 seems: (a) absolutely necessary in non-COPD hypoxemics, especially if total lung capacity (TLC) and/or residual volume (RV) are significantly reduced; (b) not absolutely necessary in COPD hypoxemics, provided they have an enlarged TLC and/or a very expanded RV; (c) advisable in intermediate situations, e.g., in COPD hypoxemics with an associated restrictive disorder caused by heart failure, congestion of pulmonary bed, parenchymal or rib cage disease, in order to establish the optimal concentration of oxygen for each patient and to avoid severe nocturnal hypoxemia without producing a dangerous rise in PaCO2.