Primary immunodeficiency-related bronchiectasis in adults: comparison with bronchiectasis of other etiologies in a French reference center.

BACKGROUND: Bronchiectasis is a heterogeneous disease depending on etiology. It represents the most frequent non-infectious pulmonary complication of primary immunodeficiencies (PID). We investigated whether bronchiectasis associated with PID had a distinct course in comparison to bronchiectasis of other causes. METHODS: Retrospective single-center study of adult patients diagnosed with non-cystic fibrosis bronchiectasis with more than 5 years of follow-up and at least 4 pulmonary functional tests available at one year apart. They were divided into three groups: PID- related bronchiectasis, idiopathic/post infectious-related bronchiectasis and other causes of bronchiectasis. Respiratory functional data and clinical outcomes were compared. RESULTS: Of 329 patients with bronchiectasis diagnosed in Foch Hospital (Suresnes, France), 98 patients fulfilled the selected criteria (20 PID-related cases, 39 idiopathic or post-infectious cases, and 39 cases with other causes). Median time of follow-up was 9.5 years. Groups were similar concerning initial characteristics (female 70.4%, never smokers 59.2%, mild severity bronchiectasis according to the FACED score and median FEV1 at diagnosis 73.5% predicted values [Q1-Q3: 53.75-90.5]), except PID patients who were younger (median age of 51.5 vs 62 years, p = 0.02). Eighty-five percent of PID patients received immunoglobulin substitution (median trough level was measured at 10.5 g/dl [10;10.92]). Global median FEV1 annual decline was 25.03 ml/year [8.16;43.9] and 19.82 ml/year [16.08;48.02] in the PID patients group. Forty-five percent of patients had bacterial colonization, pneumoniae occurred in 56% of patients and median exacerbation annual rate was 0.8 [0.3-1.4]. Hemoptysis occurred in 31.6% of patients. Global mortality rate was 11.2%. We did not record any significant difference for all clinical and functional outcomes between patients with PID and other etiologies. The median decline in FEV1 was similar in the three groups. CONCLUSIONS: The course of PID-related bronchiectasis was similar to bronchiectasis of other causes. Provided that patients receive immunoglobulin replacement, the course of PID-related bronchiectasis seems to be independent of the underlying immune disorder.

Lorlatinib - Induced pulmonary arterial hypertension.

We report here the first cases, to our knowledge, of pulmonary arterial hypertension induced by lorlatinib. It s the first time that a tyrosine kinase inhibitor for lung cancer is associated with pulmonary arteriel hypertension.

Respiratory Complications Lead to the Diagnosis of Chronic Granulomatous Disease in Two Adult Patients.

Chronic granulomatous disease (CGD) is a primary immunodeficiency associated to multiple life-threatening bacterial and fungal infections, beginning in childhood. There are rare cases of diagnosis in adulthood. We describe here two cases of late diagnosis in adults: a 45-year-old woman and 59-year-old-man. CGD diagnosis should be considered in adult patients with unexplained infectious diseases with tissue granuloma.

Pulmonary manifestations in adult patients with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by failure of superoxide production in phagocytic cells. The disease is characterised by recurrent infections and inflammatory events, frequently affecting the lungs. Improvement of life expectancy now allows most patients to reach adulthood. We aimed to describe the pattern of pulmonary manifestations occurring during adulthood in CGD patients. This was a retrospective study of the French national cohort of adult patients (≥16 years old) with CGD. Medical data were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds of adult patients. Their incidence was significantly higher than in childhood (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per year per patient) and asymptomatic in 37% of the cases. They often required lung biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned 28% of adult patients, frequently associated with a concomitant fungal infection (40%). They were more frequent in patients with the X-linked form of CGD. Immune-modulator therapies were required in most cases (70%). Respiratory manifestations are major complications of CGD in adulthood. Noninfectious pulmonary manifestations are as deleterious as infectious pneumonia. A specific respiratory monitoring is necessary.

Thoracic radiographic and CT findings of multicentric Castleman disease in HIV-infected patients.

Multicentric HIV-related Castleman disease (MCD) is a rare and severe disorder of lymphoid tissue inducing high-grade fever, hepatosplenomegaly, and diffuse peripheral lymphadenopathy. During clinical exacerbations, bilateral interstitial pneumonia may occur. In this pictorial essay, we describe different thoracic imaging of MCD, with particular emphasis on computed tomography findings, in 13 HIV-infected patients with histologically proved MCD.

Telemetric monitoring of pulmonary function after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Late-onset noninfectious pulmonary complications (LONIPC) are both frequent and severe after allogeneic hematopoietic stem cell transplantation (HSCT). The high mortality rate (40-80%) may be related to delayed diagnosis. We assessed the use of telemetric home surveillance of pulmonary function for early diagnosis of LONIPC in transplant recipients. METHODS: This prospective study monitored pulmonary function in 37 allogeneic HSCT recipients. About 3 months after HSCT, they received a portable spirometer that measured forced vital capacity, forced expiratory volume per second, and midexpiratory flow 25-75 (MEF25-75). Data were transmitted twice weekly by telephone. Conventional plethysmography confirmed any significant deterioration (>20%). RESULTS: Thirteen episodes of spirometric deterioration were detected by telemetry in 11 patients during a median 17-month (4-41) follow-up period after transplantation. In these cases, examinations including spirometry, high-resolution thoracic computed tomography and bronchoalveolar lavage diagnosed LONIPC in eight episodes in seven patients (cumulative incidence 23.4%, SE 0.08, at month 24 after transplant): bronchiolitis obliterans (BO, n=3), interstitial pneumonia (IP, n=4), or both BO and IP (n=1). Five episodes improved and three were stabilized with increased immunosuppressive therapy. At the last follow-up, of the seven patients with LONIPC, one successfully stopped immunosuppressive therapy, two were receiving low-dose mycophenolate mofetil, and four were receiving low-dose corticosteroid therapy. There were no cases of respiratory failure and no patient died from LONIPC. CONCLUSION: Telemetric home monitoring of pulmonary function is a useful procedure for early diagnosis of LONIPC before clinical pulmonary symptoms and may improve outcome after allogeneic HSCT.

Acute eosinophilic pneumonia after allogeneic hematopoietic stem cell transplantation.

A 55-year old woman with multiple myeloma was treated with hematopoietic stem cell transplantation (HSCT). She developed cutaneous and hepatic graft-vs-host disease (GVHD). Sixty-five days after HSCT, acute respiratory failure occurred. A thoracic computed tomography scan showed bilateral patchy infiltrates. Bronchoalveolar lavage revealed 40% eosinophils on differential cell count with no infectious pathogens. These findings were in favor of acute eosinophilic pneumonia. High-dose steroid treatment was started, which had a rapid and lasting favorable course. After HSCT, clinicians should be aware that acute eosinophilic pneumonia mimics infectious pneumonitis and can be associated with GVHD.