[Tracheobronchial involvement in relapsing polychondritis and differential diagnoses]. / Atteinte trachéo-bronchique de la polychondrite atrophiante et diagnostics différentiels.

Relapsing polychondritis is a systemic auto-immune disease that mainly affects cartilage structures, progressing through inflammatory flare-ups between phases of remission and ultimately leading to deformation of the cartilages involved. In addition to characteristic damage of auricular or nasal cartilage, tracheobronchial and cardiac involvement are particularly severe, and can seriously alter the prognosis. Tracheobronchial lesions are assessed by means of a multimodal approach, including dynamic thoracic imaging, measurement of pulmonary function (with recent emphasis on pulse oscillometry), and mapping of tracheal lesions through flexible bronchoscopy. Diagnosis can be difficult in the absence of specific diagnostic tools, especially as there may exist a large number of differential diagnoses, particularly as regards inflammatory diseases. The prognosis has improved, due largely to upgraded interventional bronchoscopy techniques and the development of immunosuppressant drugs and targeted therapies, offering patients a number of treatment options.

Low-cost air quality portable sensors and their potential use in respiratory health.

Air pollution is an environmental risk for the general population and for patients with various diseases, particularly respiratory diseases. Little data are available on personal exposure, but the recent emergence of low-cost air quality sensors (LCSs) should enable a better understanding of the health impacts of air pollution at the individual level. However, the reliability and accuracy of most sensors in the market have not been established, and a thorough understanding of their strengths and limitations is needed. We therefore conducted a review to address the following questions: 1) What is an LCS and what is the extent of its possible application? 2) Is the data obtained a reliable indicator of exposure? 3) What are the advantages and disadvantages of LCSs? 4) Could LCSs be useful in investigating the impact of air pollution on respiratory health? Further studies are needed to promote the use of LCS in research settings and among respiratory patients. This will allow us to monitor exposure levels, provide alerts and study the respiratory effects of individual-level air pollution.

[Interventionnal bronchoscopy for the treatment of tracheobronchomalacia]. / Place de la bronchoscopie interventionnelle dans la prise en charge des trachéobronchomalacies.

Tracheobronchomalacia is usually characterized by more than 50% expiratory narrowing in diameter of the trachea and the bronchi. The expiratory collapse includes two entities: (1) the TBM related to the weakness of the cartilaginous rings, and (2) the Excessive Dynamic Airway Collapse (EDAC) due to the excessive bulging of the posterior membrane. Patients have nonspecific respiratory symptoms like dyspnea and cough. Diagnosis is confirmed by dynamic tests: flexible bronchoscopy and/or computed tomographic scan of the chest. There are different forms of tracheobronchomalacia in adults: primary (genetic, idiopathic) or secondary to trauma, tracheotomy, intubation, surgery, transplantation, emphysema, infection, inflammation, chronic bronchitis, extrinsic compression; or undiagnosed in childhood vascular rings. Some management algorithms have been proposed, but no specific recommendation was established. Only symptomatic patients should be treated. Medical treatments and noninvasive positive pressure ventilation should be the first line therapy, after evaluation of various quality measures (functional status, performance status, dyspnea and quality of life scores). If symptoms persist, therapeutic bronchoscopy permits: (1) patient's selection by stent trial to determine whether patient benefit for surgical airway stabilization; (2) malacic airways stenting in patients who are not surgical candidates, improving QOL despite a high complication rate; (3) the management of stent-related complication (obstruction, plugging, migration granuloma); (4) alternative therapeutics like thermo-ablative solution. Lasty, the development of new types of stents would reduce the complication rates. These different options remained discussed.

Two-year follow-up of 196 interstitial lung disease patients after ICU stay.

OBJECTIVE: Interstitial lung diseases (ILDs) are associated with poor prognosis in the intensive care unit (ICU). We aimed to assess factors associated with hospital mortality in ILD patients admitted to the ICU and to investigate long-term outcome.MATERIAL AND METHODS: This was a retrospective study in a teaching hospital specialised in ILD management. Patients with ILD who were hospitalised in the ICU between 2000 and 2014 were included. Independent predictors of hospital mortality were identified using logistic regression.RESULTS: A total of 196 ILD patients were admitted to the ICU during the study period. Overall hospital mortality was 55%. Two years after ICU admission, 70 (36%) patients were still alive. Of the 196 patients, 108 (55%) required invasive mechanical ventilation, of whom 21 (20%) were discharged alive from hospital. Acute exacerbation of ILD and multi-organ failure were highly associated with hospital mortality (OR 5.4, 95% CI 1.9-15.5 and OR 12.6, 95% CI 4.9-32.5, respectively).CONCLUSION: Hospital mortality among ILD patients hospitalised in the ICU was high, but even where invasive mechanical ventilation was required, a substantial number of patients were discharged alive from hospital. Multi-organ failure could lead to major ethical concerns.

Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD. RESULTS: Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years. CONCLUSIONS: Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years.

[The effect of air pollution in diffuse interstitial lung disease]. / Rôle de la pollution au cours des pneumopathies interstitielles diffuses.

Few studies have examined the effects of air pollution in diffuse interstitial lung disease and they have focused on small numbers of patients. Most data are available in idiopathic pulmonary fibrosis and studies suggest that the level of exposure to pollutants may influence the development of acute exacerbations (ozone and NO2), their incidence (NO2), decline in respiratory function (PM10) and death (PM10 and PM2.5). Several studies show an increase in the incidence of rheumatoid arthritis in people living near busy roads. In systemic scleroderma, hypersensitivity pneumonitis and sarcoidosis although negative effects of pollution have been reported the data are insufficient to be conclusive. Nevertheless, the observed effects of air pollution are consistent with those described for other chronic respiratory diseases. Exposure to pollution induces oxidative stress, chronic inflammation and shortening of telomeres, which are all mechanisms described in fibrogenesis. New epidemiological studies are needed with individual measurements of exposure to outdoor and indoor pollution, as well as fundamental studies to clarify the effect of pollution on fibrogenesis.

[Can nivolumab be used safely in idiopathic pulmonary fibrosis?] / Le nivolumab peut-il être utilisé dans les fibroses pulmonaires idiopathiques ?

Anti-PD1 immunotherapies have become an essential treatment for bronchial cancer. According to published studies, PD1 and PD-L1 inhibitors have a better toxicity profile than chemotherapy. Nevertheless, some immune related toxicities can be potentially severe, such as induced interstitial lung disease (ILD). Currently, ILD patients are excluded from clinical trials using immunotherapy in lung cancer. IPF is the most frequent and severe form of ILD. Lung cancer represents a major complication of this disease and to date few data exist on the safety of immunotherapy in this context. We report 3 cases of IPF with lung cancer treated by nivolumab. All had a clinically mild to moderate IPF. The patients had received at least one line of chemotherapy before nivolumab and had progressive, metastatic lung cancer. Two patients experienced rapid cancer progression without immune toxicities. The third had a partial response but developed grade III immune colitis that led to discontinuation of the treatment. None developed lung toxicity or worsening of IPF on CT during follow-up, and death was always related to progression of the cancer. In our series of three patients with IPF, nivolumab was well tolerated with regard to their pulmonary condition. As inflammation and autoimmunity are probably marginal mechanisms in the pathogenesis of IPF, we do not believe that the presence of IPF should definitely disqualify potential candidates for treatment with nivolumab. Decisions should be taken, case-by-case, in selected patients without severe IPF and with no evidence of autoimmunity. In view of the epidemiology of lung cancer in IPF and the critical role of immunotherapy in the management of lung cancer, studies of prospective cohorts are urgently needed in this population.

[Treatment of sarcoidosis]. / Traitement de la sarcoïdose.

Sarcoidosis is a common disorder with heterogeneous severity. Corticosteroids are the cornerstone of its treatment and allow a disease remission but only with a suspensive effect. Immunosuppressive drugs, hydroxychloroquine and infliximab may be useful in some patients. Half of the patients recover spontaneously without any treatment. In the remaining patients, a treatment is necessary either at presentation or during the follow-up in the presence of a disease flare. Treatment duration should be of at least 12 months. The main indications of a systemic treatment include ophthalmologic, neurologic, cardiovascular, renal, laryngeal involvements, severe pulmonary manifestations, lupus pernio and marked hypercalcaemia. Initially, patients should receive prednisone or prednisolone at 0.5 to 1 mg/kg daily for 6 to 12 weeks to obtain a complete remission, and then followed by a gradual dose reduction every 6 to 12 weeks. After treatment completion, a 36-month duration monitoring is warranted to confirm recovery. Low-dose methotrexate and azathioprine are the most useful immunosuppressive drugs and are indicated in patients with of failure or contra-indication of corticosteroids or in those patients who needs a long term prednisone dose higher than 10 mg daily to control the sarcoidosis. Cyclophosphamide used is severe neurologic or heart involvement that is resistant to corticosteroids and other immunosuppressive drugs. Hydroxychloroquine and chloroquine are indicated in extensive skin lesions or as corticosteroids sparing agents. Infliximab can be useful in some severe sarcoidosis patients refractory to classical treatment, except for cardiac involvement. Topical corticosteroids can be used for limited skin involvement, anterior uveitis or cough. In the future, a more individualized treatment could be drawn from pharmacogenetic studies. The key point remains the availability of etiologic or innovative drugs for sarcoidosis refractory to currently available therapy.