Obstructive lung diseases, such as chronic obstructive pulmonary disease, asthma, or non-cystic fibrosis bronchiectasis, share some major pathophysiological features: small airway involvement, dysregulation of adaptive and innate pulmonary immune homeostasis, mucus hyperproduction, and/or hyperconcentration. Mucus regulation is particularly valuable from a therapeutic perspective given it contributes to airflow obstruction, symptom intensity, disease severity, and to some extent, disease prognosis in these diseases. It is therefore crucial to understand the mucus constitution of our patients, its behavior in a stable state and during exacerbation, and its regulatory mechanisms. These are all elements representing potential therapeutic targets, especially in the era of biologics. Here, we first briefly discuss the composition and characteristics of sputum. We focus on mucus and mucins, and then elaborate on the different sample collection procedures and how their quality is ensured. We then give an overview of the different direct analytical techniques available in both clinical routine and more experimental settings, giving their advantages and limitations. We also report on indirect mucus assessment procedures (questionnaires, high-resolution computed tomography scanning of the chest, lung function tests). Finally, we consider ways of integrating these techniques with current and future therapeutic options. Cystic fibrosis will not be discussed given its monogenic nature.
We report here the observation of a 60-year-old male jeweller who was suffering from severe asthma. Asthma onset was reported by age 30. The patient also reported comorbid severe chronic rhinosinusitis with nasal polyposis since adolescence. Aspirin and nonsteroidal anti-inflammatory drug intolerance was considered to worsen the patient's asthma symptoms, since he had experienced one episode of emergency room attendance shortly after aspirin ingestion. Episodes of generalised chronic urticaria led to genuine anaphylactic reactions that were treated with epinephrine twice in the past, but fortunately without the need for orotracheal intubation. No trigger for these episodes could be identified despite appropriate provocation tests.
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Purpose: Asthma exacerbations are inflammatory events that rarely result in full hospitalization following an ER visit. Unfortunately, certain patients require prolonged support, including occasional external lung support through ECMO or ECCOR (with subsequent further exposure to other life-threatening issues), and some die. In parallel, biologics are revolutionizing severe asthma management, mostly in T2 high patients.
Methods:We extensively reviewed the current unmet needs surrounding ICUadmitted asthma exacerbations, with a focus on currently available drugs and the underlying biological processes involved. We explored whether currently available T2-targeting drugs can reasonably be seen as potential players not only for relapse prevention but also as candidate drugs for a faster resolution of such episodes. The patient's perspective was also sought.Results: About 30% of asthma exacerbations admitted to the ICU do not resolve within five days. Persistent severe airway obstruction despite massive doses of corticosteroids and maximal pharmacologically induced bronchodilation is the main cause of treatment failure. Previous ICU admission is the main risk factor for such episodes and may eventually be considered as a T2 surrogate marker. Fatal asthma cases are hallmarked by poorly steroid-sensitive T2-inflammation associated with severe mucus plugging. New, fast-acting T2-targeting biologics (already used for preventing asthma exacerbations) have the potential to circumvent steroid sensitivity pathways and decrease mucus plugging. This unmet need was confirmed by patients who reported highly negative, traumatizing experiences.
Conclusions:There is room for improvement in the management of ICU-admitted severe asthma episodes. Clinical trials assessing how biologics might improve ICU outcomes are direly needed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.