Impact of targeted pulmonary arterial hypertension therapies in severe pulmonary hypertension in chronic lung diseases.

Research questions: Patients with severe pulmonary hypertension associated with chronic lung disease have a poor prognosis. Targeted pulmonary arterial hypertension therapies might improve exercise capacity and outcome, but there are no guidelines on treatments which are not recommended because of an unproven benefit, with discordant results from few studies in this context. The aim of our study was to evaluate targeted pulmonary arterial hypertension therapies for severe group 3 pulmonary hypertension patients. Study design and methods: We conducted an observational retrospective monocentre study on patients with severe group 3 pulmonary hypertension diagnosed on right heart catheterisation treated with targeted therapies. Primary outcome was an improvement of the distance on 6-min walk test of ≥30 m. Secondary end-points included changes in haemodynamics (pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP)) and identification of potential predictive factors of therapeutic response. Results: 139 patients were enrolled. Most patients had monotherapy with phosphodiesterase 5 inhibitors (n=128; 92%). Mean change in 6-min walk distance was +1.5 m after treatment (p=0.59). Forced expiratory volume in 1 s and forced vital capacity were not predictive factors for response. We found a significant improvement of PVR and mPAP of -1.0 Wood Units (p<0.001) and -4 mmHg (p<0.001), respectively, under treatment. 18% of patients had to withdraw treatment for intolerance. Treatment duration <3 months was associated with poor survival (hazard ratio 2.75, p=0.0005). Conclusion: Oral targeted pulmonary arterial hypertension therapies do not improve exercise capacity in patients with severe pulmonary hypertension associated with chronic lung disease, but could improve haemodynamic parameters.

Basophil Activation Test With Aspergillus Molecules: The Case for ABPA.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is an underestimated allergic disease due to Aspergillus fumigatus (AF). The main diagnostic criteria for ABPA rely on the evaluation of immunoglobulin (Ig) E and IgG responses to AF extracts, although these cannot discriminate AF-sensitization from ABPA. Objectives: To evaluate the performance of cellular functional assays with extract and molecular AF allergens in ABPA. Methods: A prospective cohort of 67 patients (6 ABPA) was investigated with basophil activation test (BAT) with AF extract. Twelve patients were further investigated for BAT responses to molecular AF components: Asp f 1, Asp f 2, Asp f 3, Asp f 4, and Asp f 6. Results: BAT with AF extract with an optimized cutoff displayed 100% sensitivity and 77.6% specificity for ABPA diagnosis. Among patients with positive BAT to AF, BAT with Asp f 4 was significantly higher in ABPA patients at 10 ng/mL (mean basophil stimulation index 10.56 in ABPA vs. 1.24 in non-ABPA patients, p = 0.0002). Conclusion: BAT with AF is a promising diagnostic biomarker in the context of suspected ABPA, which can be further improved with AF molecular allergens, especially Asp f 4.

Environmental triggers and avoidance in the management of asthma.

Identifying asthma triggers forms the basis of environmental secondary prevention. These triggers may be allergenic or nonallergenic. Allergenic triggers include indoor allergens, such as house dust mites (HDMs), molds, pets, cockroaches, and rodents, and outdoor allergens, such as pollens and molds. Clinical observations provide support for the role of HDM exposure as a trigger, although avoidance studies provide conflicting results. Molds and their metabolic products are now considered to be triggers of asthma attacks. Pets, dogs, and especially cats can undoubtedly trigger asthmatic symptoms in sensitized subjects. Avoidance is difficult and rarely adhered to by families. Cockroach allergens contribute to asthma morbidity, and avoidance strategies can lead to clinical benefit. Mouse allergens are mostly found in inner-city dwellings, but their implication in asthma morbidity is debated. In the outdoors, pollens can induce seasonal asthma in sensitized individuals. Avoidance relies on preventing pollens from getting into the house and on minimizing seasonal outdoor exposure. Outdoor molds may lead to severe asthma exacerbations. Nonallergenic triggers include viral infections, active and passive smoking, meteorological changes, occupational exposures, and other triggers that are less commonly involved. Viral infection is the main asthma trigger in children. Active smoking is associated with higher asthma morbidity, and smoking cessation interventions should be personalized. Passive smoking is also a risk factor for asthma exacerbation. The implementation of public smoking bans has led to a reduction in the hospitalization of asthmatic children. Air pollution levels have been linked with asthmatic symptoms, a decrease in lung function, and increased emergency room visits and hospitalizations. Since avoidance is not easy to achieve, clean air policies remain the most effective strategy. Indoor air is also affected by air pollutants, such as cigarette smoke and volatile organic compounds generated by building and cleaning materials. Occupational exposures include work-exacerbated asthma and work-related asthma.

[How to consider triggers and comorbid conditions in severe asthma in adults]. / Comment considérer et prendre en charge les facteurs favorisants et les comorbidités dans l'asthme sévère de l'adulte ?

Triggers and precipitating factors as well as comorbid conditions are associated with asthma and severe asthma. They interfere with the potential to control the disease and represent an additional burden for the patients. Allergen exposure is well known to induce loss of control and exacerbations. Comorbid conditions belong to various fields of medicines including cardiovascular diseases, osteoporosis, obesity and sleep apneas and GERD. They should be diagnosed and treated for themselves according to the best state of the art. Their precise role et their contribution to severe asthma pathophysiology is largely unknown and longitudinal cohort studies are needed to better understand and treat the patients with severe asthma.