Hélène Salvator

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. Pulmonary involvement is a major concern in adult CGD patients, making specific respiratory monitoring necessary http://ow.ly/FjaRS

Chronic Granulomatous Disease in Patients Reaching Adulthood: A Nationwide Study in France

Background Although prognosis of Chronic Granulomatous Disease (CGD) has greatly improved, few studies have focused on its long-term outcome. We studied the clinical course and sequelae of CGD patients diagnosed before age 16, at various adult time points. Method Cross-sectional French nationwide retrospective study of patients screened through the National Reference Center for Primary Immunodeficiencies (CEREDIH) registry. Results Eighty CGD patients (71 males [88.7%], 59 X-linked [73.7%], median age 23.9 years [minimum, 16.6; maximum, 59.9]) were included, Median ages at diagnosis and last follow-up were 2.52 and 23.9 years, respectively. Seven patients underwent hematopoietic stem cell transplantation. A total of 553 infections requiring hospitalization occurred in 2017 patient-years. The most common site of infection was pulmonary (31%). Aspergillus spp. (17%) and Staphylococcus aureus (10.7%) were the commonest pathogens. A total of 224 inflammatory episodes occurred in 71 patients, mainly digestive (50%). Their characteristics as well as their annual frequency did not vary before and after age 16. Main sequelae were a small adult height and weight and mild chronic restrictive respiratory failure. At age 16, only 53% of patients were in high school. After age 30 years, 9/13 patients were working. Ten patients died during adulthood. Conclusions Adult CGD patients displayed similar characteristics and rates of severe infections and inflammatory episodes that those of childhood. The high rate of handicap has become a matter of medical and social consideration. Careful follow-up in centers of expertise is strongly recommended and an extended indication of curative treatment by HSCT should be considered.

Comparison of outcome measures in allergic rhinitis in children, adolescents and adults.

Grass pollen‐induced allergic rhinoconjunctivitis (AR) is very common worldwide. However, its symptoms may vary with the patients age. The present study compared symptom profiles and quality of life (QoL) in children, adolescents and adults with grass pollen‐induced AR.

In allergic rhinitis, work, classroom and activity impairments are weakly related to other outcome measures

The impact of grass pollen‐induced allergic rhinitis (AR) on classroom/work productivity and activities can be assessed with a specific instrument: the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI‐AS). This study evaluated the relationships between the WPAI‐AS and other outcome measures in AR.

Chronic beryllium disease: azathioprine as a possible alternative to corticosteroid treatment

To the Editor: Chronic beryllium disease (CBD) is a chronic granulomatous disease that mainly affects the lungs. It occurs after beryllium exposure in genetically susceptible individuals with, most commonly, the HLA-DPβ1 (Glu69) polymorphism [1]. Beryllium particles are slowly washed out, causing delayed onsets of the disease and flare ups long after exposure to beryllium [2, 3]. The clinical, radiological and pathological presentation of CBD is very similar to sarcoidosis. Thus, misdiagnosis is not uncommon, as reported by Fireman et al . [4] and Muller-quernheim et al. [5]. These authors managed to correct the diagnosis of chronic sarcoidosis to CBD in 4–6% of patients, thanks to a careful retrospective screening for beryllium exposure [4, 5]. In CBD, lungs are damaged by diffuse noncaseating granulomas and this may lead to fibrosis. The US Beryllium Case Registry determined the following specific criteria for CBD diagnosis: a beryllium exposure history; relevant clinical and radiological signs (breathlessness, reduced pulmonary capacity and diffuse interstitial opacities); evidence of beryllium sensitisation with positive beryllium lymphocyte proliferation test in blood or in bronchoalveolar lavage (BAL); and histopathological features such as noncaseating granulomas or mononuclear tissue infiltration without any infection. Long-term prognosis of CBD is poor with a mortality rate ranging from 5.8% …

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.

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.

Pulmonary alveolar proteinosis and Mycobacterium abscessus lung infection related to ruxolitinib after allogeneic stem cell transplantation

Non-infectious pulmonary complications are frequent after allogeneic haematopoietic stem cell transplantation (HSCT). They mainly comprise bronchiolitis obliterans and interstitial pneumonia in the setting of chronic graft-versus-host disease (cGVHD) [1]. Ruxolitinib may induce pulmonary alveolar proteinosis and favour respiratory non-tuberculous mycobacterial infections http://ow.ly/bTXn30jogC8

ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) relatead to sirolimus-eluting stent

Background: Hypersensitivity reactions have been reported after sirolimus-eluting stent implantation. We report the first case of ANCA-negative EGPA related to a coronary stent. Case report: A 58-yrs old former smoker patient was admitted in our Department in 2012.He was well until 2006. Because of an acute coronary syndrome a sirolimus eluting stent (Cypher *) was implanted. A few hours after implantation, the patient complained of dyspnea. Asthma was diagnosed. Eosinophilia (1000/mm3) and increased IgE serum level (426k UI/L) were noted.No ANCA were detected.He was treated with inhaled corticosteroids and bronchodilatators, then omalizumab.During the four years, the pulmonary worsened.Oral prednisone (8mg/d) was administered with montelukast. In 2012, when admitted in our Department, FEV1 vas 19% and FEV1/VC at 39%. Renal and hepatic function tests were normal.No auto-antibodies were detected.IgE level was 173 kUI/L. Thoracic CT-scan disclosed bilateral bronchiectasis in the two lower lobs. Sinusal scan showed paranasal sinus thickening. A nasal biopsy exhibited a vascular infiltration made up of eosinophils. A diagnosis of a forme fruste EGPA was performed. IV cyclophosphamide with increased prednisone regimen were given with immunoglobulins IV Numerous exacerbation related to bacterial infections occured worsening the pulmonary function. Methotrexate and azithromycin were added. Conclusion: Physicians should be aware that asthma and EGPA can develop after placement of cornary stent. Adverse event reports have to be submit to the health authorities because these manifestation may be under diagnosed. The polymers of the stent may be the cause of these manifestations.

Stratégie thérapeutique au long cours dans la bronchopneumopathie chronique obstructive : comment modifier le cours de la maladie

COPD is a pulmonary disease with a systemic impact. The goals of COPD assessment are to determine the severity of the disease to guide management. Smoking cessation is a prime objective at all the stages of the disease to modify the long-term decline in lung function, reduce the COPD symptoms, and the frequency of exacerbations, improve health status and reduce mortality. The bronchodilators are central in the pharmacologic management of COPD. Long-acting bronchodilators are indicated as maintenance treatment to relieve COPD symptoms (particularly dyspnea) despite regular use of short-acting bronchodilators. Long-acting bronchodilators reduce the exacerbation rate. The choice between a long-acting β2-adrenergic and an anticholinergic depends on the patients perception of symptom relief. The inhaled corticoids are only indicated in COPD combined with long-acting β2-adrenergic in patients with severe COPD and a history of repeated exacerbations, who have significant symptoms despite therapy with bronchodilators. The combination of an inhaled corticosteroid with a long-acting β2-agonist reduces the exacerbation rate. The rehabilitation should be offered to all patients with dyspnea, exercise intolerance, or limitation in everyday activities related to COPD despite optimal pharmacological therapy and management of co-morbidities. Pulmonary rehabilitation is a multidisciplinary and tailored management of the COPD patients which enable to optimize exercise capacity, social reintegration, autonomy, reduce health care costs by decreasing the exacerbation rate, urgent visits and duration of hospitalisation. The rehabilitation is not just focusing on the improvement of exercise capacity, but also seeks sustained behavioural changes that are needed to achieve real improvement in health status and quality of life. Pulmonary rehabilitation is also an excellent opportunity for education which is critical in the healthcare pathway.