Will the asthma revolution fostered by biologics also benefit adult ICU patients?

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 ICU-admitted 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.

Patient distrust in pharmaceutical companies: an explanation for women under-representation in respiratory clinical trials?

BACKGROUND: Patient skepticism concerning medical innovations can have major consequences for current public health and may threaten future progress, which greatly relies on clinical research. The primary objective of this study is to determine the variables associated with patient acceptation or refusal to participate in clinical research. Specifically, we sought to evaluate if distrust in pharmaceutical companies and associated psychosocial factors could represent a recruitment bias in clinical trials and thus threaten the applicability of their results. METHODS: This prospective, multicenter survey consisted in the administration of a self-questionnaire to patients during a pulmonology consultation. The 1025 questionnaires distributed collected demographics, socio-professional and basic health literacy characteristics. Patients were asked to rank their level of trust for pharmaceutical companies and indicate their willingness to participate in different categories of research (pre or post marketing, sponsored by an academic institution or pharmaceutical company). Logistic regression was used to determine factors contributing to "trust" versus "distrust" group membership and willingness to participate in each category of research. RESULTS: One thousand patients completed the survey, corresponding to a response rate of 97.5%. Data from 838 patients were analyzed in this study. 48.3% of respondents declared that they trusted pharmaceutical companies, while 35.5% declared distrust. Being female (p = 0.042), inactive in the employment market(p = 0.007), and not-knowing the name of one's disease(p = 0.010) are factors related to declared distrust. Distrust-group membership is associated with unwillingness to participate in certain categories of trials such as pre-marketing and industry-sponsored trials. CONCLUSION: Distrust in pharmaceutical companies is associated with a specific patient profile and with refusal to participate in certain subcategories of trials. This potential recruitment bias may explain the under-representation of certain categories of patients such as women in pre-marketing drug trials.

Mid-Term Sequelae of Surviving Patients Hospitalized in Intensive Care Unit for COVID-19 Infection: The REHCOVER Study.

OBJECTIVES: The objective of this prospective, single-center study was to explore the mid-term outcomes 6 to 9 months after hospitalization in an Intensive Care Unit (ICU) for severe COVID-19 infection. METHODS: Patients systematically underwent biological tests, pulmonary function tests, chest computed tomography (CT) scan, and psychological tests. RESULTS: Among 86 patients, including 71 (82.6%) men, median age of 65.8 years (56.7; 72.4), 57 (71.3%) patients presented post-COVID-19 asthenia, 39 (48.1%) muscle weakness, and 30 (36.6%) arthralgia. Fifty-two (64.2%) patients had a decreased diffusion capacity for carbon monoxide (DLCO) <80% and 16 (19.8%) had DLCO <60%. Chest CT-scans showed ground glass opacities in 35 (40.7%) patients, and reticular changes in 28 patients (33.7%), including fibrosis-like changes in 18 (21.7%) patients. Reticular changes and DLCO <60% were associated with length of stay in ICU, and reticular changes with higher maximal CRP level. The psychological questionnaires found 37.7% suffered from depression, 23.5% from anxiety, 42.4% from insomnia, and 9.4% from post-traumatic stress. Being female was associated with a higher frequency of depression and anxiety, with depression scores being associated with obesity. CONCLUSIONS: Many patients hospitalized in ICU for severe COVID-19 infection have mid-term sequelae. Additional studies on the prognostic factors seem necessary.

Health-related quality of life and disease progression in pulmonary arterial hypertension patients: a 3-year study.

OBJECTIVES: The role of health-related quality of life (HRQoL) and psychological variables in pulmonary arterial hypertension (PAH) progression remains poorly quantified. We aimed to investigate the relationship between disease progression in PAH patients and HRQoL and psychological characteristics. METHODS: A 3-year longitudinal cohort was initiated. Patients with stable PAH (groups I-IV ineligible for angioplasty/endarterectomy) were included (n=55). Standard clinical variables, including invasive haemodynamic parameters, were prospectively recorded. A battery of questionnaires was used to characterise the psychological status of patients upon study initiation, and HRQoL was quantified using the SF-36 Questionnaire every 3 months for 24 months, and then again at 36 months. Guideline-defined disease progression and progression-free survival were recorded for 36 months. MEASUREMENTS AND MAIN RESULTS: Psychological distress was highly prevalent at baseline. The Physical Component Summary (PCS) and the Mental Component Summary (MCS) of the HRQoL were poor (PCS=37.13±8.18; MCS=42.42±10.88) but stable over 3 years of follow-up. Among PCS subscales, Physical Functioning (PF) (p=0.012) was identified as being independently associated with disease progression (Cox survival model), along with mean pulmonary arterial pressure (p=0.003) and cardiac output (p=0.005). Depression was the unique independent psychological characteristic associated with PF (p=0.0001). CONCLUSIONS: PAH patients have poor HRQoL. In addition to already known criteria related to disease severity, the HRQoL PF subscale is independently associated with disease progression in PAH. This may be explained by depression.

Impact of psychological factors on the health-related quality of life of patients treated for pulmonary arterial hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare and life-threatening disease well-marked by under diagnosis, delayed diagnosis and atypical treatments. Few data are available on the quality of life (QoL) and psychosocial characteristics of patients with PAH. Our aim is to describe the impact of psychological factors on the health-related quality of life (HRQoL) of treated PAH patients in a cross-sectional study. METHODS: Consecutive patients presenting at our Competency Centre for PAH were recruited. The aetiology, New York Heart Association (NYHA) stage, haemodynamics, 6-min walk distance (6MWD), delta SPO2 (Pulse oximeter oxygen saturation; baseline lowest value during 6-min walk test (6MWT), current treatments and psychological history were recorded. HRQoL, anxiety, depression and coping strategies were explored using self-administered questionnaires (SF-36, HADS, STAI-Y, CHIP and WCC). RESULTS: A total of 55 patients were included. The HRQoL of PAH patients was poor with altered results on several scales. Anxiety and depression were high and coping was focused on medical information strategies. Multivariate analysis indicated a positive relationship between 6MWD and the Physical Composite Score for QoL (p=0.004), as well as a negative relationship between delta SPO2 and the Mental Composite Score (p=0.02), irrespective of other known prognostic factors (such as haemodynamics at right heart catheterization). Depression and Trait-Anxiety were associated with a lower physical (p=0.001) and mental (p<0.001) QoL, respectively. CONCLUSIONS: Psychological factors impact the HRQoL of treated patients. A longitudinal and qualitative study should refine these results. TRIAL REGISTRATION: Clinical trial N°: NCT01380054.

Interference of psychological factors in difficult-to-control asthma.

BACKGROUND: Most patients with asthma can be controlled with suitable medication, but 5-10% of them remain difficult to control despite optimal management. OBJECTIVE: We investigated whether patients with difficult-to-control asthma (DCA) or controlled asthma (CA) differ with respect to psychological factors, such as general control beliefs on life events. METHODS: DCA was defined as an absence of control despite optimal management. Recent control was measured using the Asthma Control Questionnaire. General control beliefs were investigated using a Locus of Control scale (LOC). RESULTS: Patients with DCA had a significantly higher external LOC as compared to patients with CA (P=0.01). In the DCA group, the hospital admission rate was highly significant in association with the external LOC (P=0.004) as compared to the internal LOC trend. CONCLUSION: This study showed that patients with DCA had different general control beliefs which might have hampered their management and interfered with their therapeutic adherence. The present findings could enhance management of DCA in a clinical setting.

[Difficult asthma]. / Asthme difficile.

Difficult asthma is a major issue in pulmonary medicine today because of its cost for patients and society. Difficult asthma is asthma that remains uncontrolled despite optimal specialist management. The validity of the diagnosis must be reconsidered in these cases: associated or differential diagnoses may be involved in the lack of control, and it is always necessary to assess the patient's treatment adhesion. Sufficient time--at least a year--must be taken to get to know the patient and to meet the objectives set. The standard asthma therapies should be tested objectively. Severe asthma is the reality of difficult asthma that endures despite a reaffirmed diagnosis, optimal compliance and controlled comorbidities. Better knowledge is needed of the pathophysiology of these patients' asthma. Improved knowledge of these phenotypes will make it possible to develop innovative treatments. They will need to be validated in clinical research for subsequent use that is wider but more rational because targeted at phenotypes likely to benefit from them.

Future treatment for asthma.

The landscape of asthma has considerably changed after 40 years of inhaled corticosteroid development and nearly 20 years since the first monoclonal antibodies (mAbs) were approved. New members of pharmacological families and more effective drug-delivery devices have been designed but the proportion of uncontrolled patients, unfortunately, remains stable. The most promising treatments now rely on targeted therapies that encourage the improvement of the characterisation of our patients. These clinical (phenotype) or new biological (endotype) tools lead to palpable personalised medicine. This review examines not only the future of mAbs and other new ways of treating asthma but also describes futuristic views based on the paradigm shifts that are ready to occur.

Severe asthma and adherence to peak flow monitoring: longitudinal assessment of psychological aspects.

BACKGROUND: Adherence in severe asthma is a difficult health problem. Although psychosocial factors may be responsible for non-adherence, few longitudinal studies have investigated their link with adherence, with most studies having focused on pharmacology. METHODS: Sixty patients with severe asthma were recruited. Adherence was electronically monitored using peak flow measurements at entry and after 1 year of follow-up. Eysenck's Personality Inventory, Rotter's Locus of Control (LOC), and health control beliefs were all studied. Multiple logistic regression (MLR) was used for risk calculations. RESULTS: Initially, subjects with poor adherence had an external LOC (P=.001) and a high extraversion score (P=.003) compared to those with good adherence. The lie score was high in all patients. Nocturnal awakenings were highly significantly correlated with poor adherence (P=.006). After 1 year, patient adherence, extraversion, and neuroticism remained unchanged. The LOC changed in subjects with poor adherence, showing a less "external" orientation (P=.007). The health parameters were better at the end of the study. By MLR analysis, externality, extraversion, and low social desirability were associated with poor adherence. Patients with poor adherence had a greater probability of nocturnal symptoms. CONCLUSION: No specific personality type was associated with lack of adherence in the present study, but a high extraversion score, a low social desirability score, and a high level of externality were all predictors of poor adherence.

[Treatment education for patients with asthma]. / Education thérapeutique du patient asthmatique.

Randomized studies show that the best results come from patient-focused educational programs based on self-management (written and individualized action plan, self-monitoring, and regular medical review). The simple provision of information about asthma does not improve health outcomes. Teenagers with asthma are the most fragile patients, because of the lack of specific management for them. Repeated sessions are recommended and educational programs, started in childhood, might make it possible to prevent or at least decrease the risks of non-adherence during adolescence. The absence of consensus on educational interventions impedes the legibility of their impact.