Background—: The French pulmonary hypertension (PH) registry allows the survey of epidemiological trends. Isolated cases of precapillary PH have been reported in patients who have chronic myelogenous leukemia treated with the tyrosine kinase inhibitor dasatinib. Methods and Results—: This study was designed to describe incident cases of dasatinib-associated PH reported in the French PH registry. From the approval of dasatinib (November 2006) to September 30, 2010, 9 incident cases treated by dasatinib at the time of PH diagnosis were identified. At diagnosis, patients had moderate to severe precapillary PH with functional and hemodynamic impairment. No other incident PH cases were exposed to other tyrosine kinase inhibitors at the time of PH diagnosis. Clinical, functional, or hemodynamic improvements were observed within 4 months of dasatinib discontinuation in all but 1 patient. Three patients required PH treatment with endothelin receptor antagonist (n=2) or calcium channel blocker (n=1). After a median follow-up of 9 months (min-max 3–36), the majority of patients did not demonstrate complete clinical and hemodynamic recovery, and no patients reached a normal value of mean pulmonary artery pressure (≤20 mm Hg). Two patients (22%) died at follow-up (1 of unexplained sudden death and 1 of cardiac failure in the context of septicemia, respectively, 8 and 12 months after dasatinib withdrawal). The lowest estimate of incident PH occurring in patients exposed to dasatinib in France was 0.45%. Conclusions—: Dasatinib may induce severe precapillary PH fulfilling the criteria of pulmonary arterial hypertension, thus suggesting a direct and specific effect of dasatinib on pulmonary vessels. Improvement is usually observed after withdrawal of dasatinib.

First recognized as an occupational disorder, obliterative bronchiolitis is now the primary noninfectious pulmonary complication of allogeneic hematopoietic stem-cell transplantation and lung transplantation. This review includes an update on recognition, treatment, and prevention.

Acute respiratory failure (ARF) in patients with cancer is frequently a fatal event. To identify factors associated with survival of cancer patients admitted to an intensive care unit (ICU) for ARF, we conducted a prospective 5-year observational study in a medical ICU in a teaching hospital in Paris, France. The patients were 203 cancer patients with ARF mainly due to infectious pneumonia (58%), but also noninfectious pneumonia (9%), congestive heart failure (12%), and no identifiable cause (21%). We measured clinical characteristics and ICU and hospital mortality rates. ICU mortality was 44.8% and hospital mortality was 47.8%. Noninvasive mechanical ventilation was used in 79 (39%) patients and conventional mechanical ventilation in 114 (56%), the mortality rates being 48.1% and 75.4%, respectively. Among the 14 patients with late noninvasive mechanical ventilation failure (>48 hours), only 1 survived. The mortality rate was 100% in the 19 noncardiac patients in whom conventional mechanical ventilation was started after 72 hours. By multivariable analysis, factors associated with increased mortality were documented invasive aspergillosis (odds ratio [OR], 2.13; 95% confidence intervals [CI], 1.05-14.74), no definite diagnosis (OR, 3.85; 95% CI, 1.26-11.70), vasopressors (OR, 3.19; 95% CI, 1.28-7.95), first-line conventional mechanical ventilation (OR, 8.75; 95% CI, 2.35-35.24), conventional mechanical ventilation after noninvasive mechanical ventilation failure (OR, 17.46; 95% CI, 5.04-60.52), and late noninvasive mechanical ventilation failure (OR, 10.64; 95% CI, 1.05-107.83). Hospital mortality was lower in patients with cardiac pulmonary edema (OR, 0.16; 95% CI, 0.03-0.72). Survival gains achieved in critically ill cancer patients in recent years extend to patients requiring ventilatory assistance. The impact of conventional mechanical ventilation on survival depends on the time from ICU admission to conventional mechanical ventilation and on the patient's response to noninvasive mechanical ventilation.

To investigate the capacity of the pulmonary vascular bed to acutely vasodilate, we examined in 35 consecutive patients with primary pulmonary hypertension (PPH), the hemodynamic effects of incremental inhalation periods of an air-NO mixture at different concentrations (10, 20, and 40 ppm), and compared them with those of an acute infusion of prostacyclin (PGI2). An individual pulmonary vasodilator response was defined by a fall in total pulmonary resistance (TPR) > or = 30% relative to mean TPR baseline value. Thirteen patients were responders and 22 were nonresponders to both drugs, and they did not significantly differ in overall baseline characteristics except for mean right atrial pressure (p < 0.03). In responders, both drugs produced similar individual vasodilator response. Changes in mean pulmonary arterial pressure and TPR observed during NO and PGI2 were closely correlated (r2 = 0.9, p < 0.001, and r2 = 0.7, p < 0.01, respectively). The vasodilator response to NO was not concentration-related with a maximal effect obtained at 10 ppm. Combination of both drugs did not lead to any additive vasodilator response. Unlike PGI2, NO did not induce any systemic effect, no adverse reaction, but a moderate increase in methemoglobin. Inhaled NO at low dose (10 ppm) appears to be an effective, safe, and reliable substitute for PGI2 in screening for acute pulmonary vasodilator responsiveness during therapeutic assessment of patients with PPH.