Immunity and COVID-19: On the path towards precision medicine?

Thomas Planté-Bordeneuve, Antoine Froidure, Charles Pilette Published in the journal : May 2020 Category : Pneumology

COVID-19, which is caused by the SARS-CoV-2 virus, induces in 5 to 15% of cases a severe phenotype with bilateral pneumonia, sometimes complicated by an acute respiratory distress syndrome and respiratory failure. Patients present with lymphopenia and possibly neutrophilia, which are of prognostic relevance. In addition, some patients develop immune overactivation, which is associated with a cytokine storm and a poor prognosis. Although the underlying mechanisms remain poorly understood, the virus’ ability to escape immune mechanisms could play an important role. An improved understanding of the disease immunopathology should help defining a precision medicine to treat COVID-19 patients based on predictive (or early) biomarkers of severity.

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Pulmonology in the era of 4P medicine

Charles Pilette, Antoine Froidure, Audrey Hanson, Thierry Pieters Published in the journal : February 2020 Category : Pneumology

Pulmonology has entered the era of so-called "4P" medicine, which is meant to be preventive, personalized, predictive, and participatory. Combating smoking and improving air quality are essential for the prevention of most respiratory diseases. The summary of innovations we offer in the fields of asthma, lung cancer, and interstitial lung disease clearly illustrates the concepts of predictive and personalized medicine. Health care now takes into account not only observable characteristics, such as asthma with sinus polyposis or non-small cell cancer, but also the mechanisms involved in their pathophysiology, such as eosinophils in asthma or PD1 / PD-L1 expression in lung cancer. All this underlies the concept of endotype. Finally, the patient is offered the appropriate treatment based on biomarkers. We also benefit from recent advances in genetics. In addition to the search for predictive rearrangements underlying the response to certain chemotherapies, the discovery of common genetic variants associated with pulmonary fibrosis will enable us to predict its evolution, or even more, prevent its occurrence by promoting preventive measures within risk groups. Finally, the inclusion of patients in the care process optimizes adherence to treatment and control of the disease, while feeding research in our University Clinics to better understand and treat medical conditions in the near future.

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Acute interstitial nephritis under pembrolizumab treatment

Romain Dury, Valentin Van Den Bossche, Kim Vanderheyde, Sophie Jossart Published in the journal : January 2020 Category : Pneumology

Pembrolizumab is a humanized monoclonal antibody targeting the PD-1 receptor expressed on the surface of cytotoxic T lymphocytes. Along with other specific antibodies, it belongs to the class of immune checkpoint inhibitors (ICI). Its use as monotherapy is particularly indicated in the first-line treatment of metastatic non-small-cell lung cancers (NSCLC) without oncogenic addition (ALK or EGFR mutations) and expressing the PD-L1 receptor at ≥50% on the surface of tumor cells, corresponding to a high tumor proportion score (TPS score), which has shown predictive of a better response to treatment (1) (2) (3). We have presented herein the case of a patient with a pembrolizumab-treated NSCLC complicated by acute interstitial nephritis (AIN) under pembrolizumab immunotherapy. Permanent discontinuation of pembrolizumab and treatment with intravenous corticosteroids enables us to gradually normalize the patient's renal function.

Nephritis is one of the rare potential undesirable effects associated with immunotherapy.

New toxicity profiles associated with immune checkpoint inhibitors require the reporting of any symptoms or biological abnormalities dedected during their use in order to initiate prompt management of these immunotherapy-related undesirable effects.

Key Words

Immunotherapy, acute interstitial nephritis, pembrolizumab, undesirable effects

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Familial pulmonary fibrosis and telomeropathies

Thomas Planté-Bordeneuve (1,2), Xavier Poiré (3), Anne De Leener (4), Antoine Froidure (1,2) Published in the journal : September 2019 Category : Pneumology

Germline mutations in genes related to telomere biology are the first cause of familial pulmonary fibrosis. The progressive shortening of these protective structures successively leads to cell cycle arrest, cellular exhaustion, and the possible development of lung fibrosis. This process may also involve hematopoiesis, the liver, and the skin. The most common pulmonary feature is an early-onset, rapidly progressive pulmonary fibrosis, leading to terminal respiratory insufficiency.

The multisystemic features, early disease onset, and familial component are key hallmarks of the disease. Diagnosis is primarily based on measuring telomere length and identifying a germline mutation. The management of the affected patients is rather complex, because of their rapidly progressive fibrosis, while the effects of antifibrotic drugs are limited, and the patients prone to develop drug-related undesirable events.

The Cliniques universitaires Saint-Luc have set up a specific program, in close collaboration with pneumologists, hematologists, and geneticists, designed to offer optimal care to this patient population.

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Cystic fibrosis: The era of CFTR modulators

Olivier Lebecque (1), Teresinha Leal (2), Patrick Lebecque (3) Published in the journal : February 2019 Category : Pneumology

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are small molecules aimed at improving CFTR function by specifically targeting the different classes of CFTR mutations. Recent Phase II studies of triple therapy, including new generation correctors, have demonstrated spectacular improvements in forced expiratory volume in 1s (FEV1), likely to translate into improved quality of life and increased life expectancy. Within the next 5 years, a highly effective CFTR modulator therapy will probably be approved for most cystic fibrosis patients, including those carrying at least one copy of the F508del mutation (88% of Belgian patients). Patients with well-preserved lungs will benefit most from these treatments.

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Spontaneous and recurrent pneumothorax revealing pulmonary Langerhans cell histiocytosis: clinical case report and literature review

Anne-Louise Kollegger(1), Vi Doan(2), Geneviève Derue(3) Published in the journal : January 2018 Category : Pneumology

Langerhans cell histiocytosis is a rare disease that at times presents as an infiltrative lung disease, especially among smokers. We have herein reported the case of a young woman, who had been treated for histiocytosis in her childhood, presenting with spontaneous pneumothorax. CT scan revealed pulmonary Langerhans cell histiocytosis. A second pneumothorax episode with a permanent air leak made surgical treatment necessary. Given that the pneumothorax recurred, with the lung failing to expand, we conducted a literature review on this issue. This review revealed pneumothorax to occur in 10-20% of adult patients presenting pulmonary histiocytosis, with a high rate of recurrence.

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Small cell neuroendocrine carcinoma of the maxillary sinus: an uncommon localization

Canelle Koutny (1), Vincent Potmans (2) Published in the journal : November 2017 Category : Pneumology

This case report describes a metastatic small cell neuroendocrine carcinoma (SCNC) of the right maxillary sinus, which first manifested as atypical low back pain. Due to the rarity of this localization, specific therapeutic recommendations for SCNC of paranasal sinuses are still lacking. Current treatment modalities are extrapolated based on similar tumors of pulmonary origin. This contribution comprises a case description, along with a review of clinical presentations, imaging characteristics, and treatments available to date. This article will eventually end with a series of practical recommendations.

Key Words

Small cell neuroendrocrine carcinoma, paranasal sinus, extra-pulmonary, metastatic

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COPD: What's new ?

E. Marchand Published in the journal : May 2016 Category : Pneumology

Chronic obstructive pulmonary disease (COPD) is a common condition, which is burdened with significant morbidity and mortality. The Global initiative for Obstructive Lung Disease (GOLD) international guidelines have recently proposed a new classification based not only on the degree of airflow limitation, but also on symptoms and risk of exacerbations.

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T. Pieters, P. Collard, C. Dahlqvist, J.P. d’Odemont, A. Froidure, S. Gohy, G. Liistro, E. Marchand, G.B. Mwenge, C. Pilette, G. Reychler, O. Vandenplas Published in the journal : February 2016 Category : Pneumology

In the field of pneumology, the year 2015 was once again rich in new developments, of which we provide a non-exhaustive list in this article. They concern pathophysiological mechanisms especially in sleep apnea, in addition to diagnostic and curative features. The diagnostic advances include the new reference values for spirometry, the contribution of cryobiopsy to the diagnosis of diffuse interstitial lung diseases, the assessment of bronchiectasis in adults, etc. Regarding treatments, we have chosen to focus on the advances in drug and non-drug management of asthma, idiopathic pulmonary fibrosis, emphysema, and bronchial cancer.

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