Innovations during 2022 in pulmonology

Charlotte Smetcoren, Gimbada Benny Mwenge, Thierry Pieters, Françoise Pirson, Gregory Reychler, Giuseppe Liistro, Sophie Gohy, Antoine Froidure, Charles Pilette Published in the journal : February 2023 Category : Pneumology

Respiratory medicine is progressively becoming a personalized care due to a better understanding of the pathophysiological mechanisms underlying the endotypes of pulmonary diseases, either frequent (sleep apnea syndrome, lung cancer, chronic obstructive pulmonary disease, asthma, and allergies) or rarer (interstitial lung diseases, cystic fibrosis), in addition to more generic care benefiting to most patients (e.g., environmental avoidance measures, physical exercise). This article describes those inspiring concepts applied to major respiratory diseases by presenting major advances made in 2022.

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Food anaphylaxis: inventory in a Belgian pneumo-allergology consultation

Aurore De Vriendt1, Françoise Pirson1,2,3,4 Published in the journal : May 2022 Category : Pneumology

Food allergy is a common condition, and anaphylaxis, which is its most severe presentation, potentially fatal. This retrospective study has described the characteristics of patients presenting with food anaphylaxis (Grade >2), who were evaluated at the Allergology Unit of Saint-Luc University Clinics, between 2017 and 2019.

The studied population comprised mainly adults, their mean age being 33.7 years. Anaphylaxis were mainly caused by mandatory allergens. The allergological work-up was chiefly based on a detailed clinical history and demonstration (in vivo or in vitro) of sensibilization, in addition to an oral food challenge in several cases. The most common culprit foods were shellfish and peanuts, both accounting for 38.7% of cases. Intramuscular epinephrine was injected in less than half of anaphylaxis cases. Acute management of food anaphylaxis is thus still inappropriate in regards to international guidelines.

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2021 innovations in pulmonology

Charles Pilette, Thierry Pieters, Antoine Froidure Published in the journal : February 2022 Category : Pneumology

In pulmonology, the year 2021 was marked by significant progress towards personalized medicine, particularly in the fields of asthma, interstitial diseases, and bronchopulmonary cancer. In asthma, the advent of anti-IgE and anti-IL-5 (and soon anti-IL-4R) biologics rendered it possible to wean a substantial number of patients off oral corticosteroids, with additional beneficial effects on exacerbations or lung function (1). It has therefore become essential to refer patients with severe asthma, especially those being corticosteroid-dependent, to a specialized center (2), where the management can either confirm or infirm the indication for a biologic agent, meaning after excluding difficult asthma causes, and then implement, as necessary, a progressive weaning protocol of oral corticosteroids (3). The department has been participating to a large European study that is designed to better define the criteria for (non)response to these biological treatments (4). In interstitial diseases, a personalization of the diagnostic and therapeutic approach is currently underway by integrating all the clinical, radiological, and biological patient characteristics. A good example to mention was the identification of mutations in the telomerase complex genes, with relevant therapeutic implications in terms of responses to anti-fibrotic treatments (5) and adaptation of immunosuppressive treatments in the event of lung transplantation (6). The department was and still is involved in conducting phenotyping studies of interstitial diseases complicating inflammatory rheumatism, in collaboration with the rheumatology department, along with fundamental explorations in mucosal immunology (7). In lung cancer, clinical studies conducted in 2021 were aimed at refining the positioning of anti-PD1/PD-L1 immunotherapy in non-small-cell bronchial cancer, with our department participating in some of them in its cancer center. Finally, the department remained involved in the management of COVID patients, and as a reference center for immuno-allergological reactions and contraindications to vaccines, as well (8).

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Acute respiratory distress in relation to COVID-19 and beyond

Charles Pilette, Grégory Reychler, Nicolas Audag, Anne-Claire Latiers, Stéphanie Quennery, William Poncin, Gimbada Mwenge, Giuseppe Liistro, Charlotte Smetcoren, Frank Aboubakar, Sophie Gohy, Silvia Berardis, Antoine Froidure Published in the journal : February 2021 Category : Pneumology

In 2020, COVID-19 mobilized pulmology experts along with other colleagues specializing in infectious diseases, emergency physicians, as well as intensivists. This occurred within a concerted effort, especially with the aim to reach a consensus in managing the infectious and inflammatory diseases at Cliniques Universitaires Saint-Luc. The physiotherapy team was mobilized from the very first hours of the pandemic; they were indeed involved in optimizing respiratory care for these patients. Original work and the "field" experience of our physicians and physiotherapists turned out to be instrumental in clarifying essential concerns. These latter included the best interface for delivering high-flow oxygen therapy, as well as the usefulness of supplying positive pressure continuous positive airway pressure (CPAP) to numerous patients with severely hypoxemic SARS-CoV-2 pneumonia, in addition to defining the most appropriate aerosol therapy in this pandemic context.

The follow-up of chronic respiratory disease-affected patients represented another challenge. Indeed, we were obliged to implement alternative methods, including teleconsultations, which particularly applied to the first CONIV-19 wave. Nevertheless, the year 2020 witnessed the arrival on the European market of targeted cystic fibrosis therapies as well as self-injectable biologics for severe Type 2 asthma, along with the multidisciplinary management of the ever-increasing number of cases suffering from diffuse interstitial pathologies. Notably, our department distinguished itself through original COVID-19 studies that were conducted in respiratory disease (cystic fibrosis, severe asthma patients) patient cohorts. Another distinctive feature pertaining to our department was the shedding light on the aging mechanisms involved in certain genetic pulmonary fibrosis forms, as well as on telomere length regulation, the latter being a risk factor for COVID-19 severity. Lastly, while lung cancers remain at the top of the "serial killer" list, these gloomy statistics are likely to change in the near future, owing to the progress made in molecular biology. This progress enables us today, and will do it even more tomorrow, to initiate and implement a personalized medicine management for certain cancer types.

These clinical and research transfer activities clearly demonstrate the pulmologists’ desire to work at the patient's bedside, in an effort to offer him the most appropriate specific care, in line with our academic hospital’s missions. This latter includes an active contribution to further developing medical and scientific knowledge in this field. Notably, this issue is at the heart of the 2020 news.

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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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