Changes in the physical and affective dimensions of dyspnoea after a home-based pulmonary rehabilitation in fibrotic idiopathic interstitial pneumonias.

Background: Our objective was to evaluate the short-, medium- and long-term benefits of home-based pulmonary rehabilitation (PR) on the physical and affective components of dyspnoea in people with fibrotic idiopathic interstitial pneumonias (f-IIPs). Anxiety and depressive symptoms, fatigue, health-related quality of life and exercise tolerance were also assessed. Methods: Data on 166 individuals with f-IIPs who enrolled in an 8-week home-based PR programme (weekly supervised 90-min session) were retrospectively analysed. Assessments included the Dyspnoea-12 (D-12) questionnaire, Hospital Anxiety and Depression Scale, Fatigue Assessment Scale, Visual Simplified Respiratory Questionnaire and 6-min stepper test, and were performed at home at short, medium (6 months) and long (12 months) term. Results: Among the 166 individuals with f-IIPs who enrolled in PR, 75 (45%) and 91 (55%) participants had a diagnosis of idiopathic pulmonary fibrosis and fibrosing non-specific interstitial pneumonia, respectively, and 87 (52%) participants concluded a full year of follow-up. In the total group, both physical and affective components of dyspnoea were improved, at short, medium and long term, after PR. Overall, half of the participants reached the minimally important difference of 3 points of the D-12 questionnaire at the end of PR, and at the 6- and 12-month follow-ups. Anxiety and depressive symptoms, fatigue and health-related quality of life were also improved, while the short-term benefits in exercise tolerance were not maintained 1 year after PR. Conclusion: An individualised home-based PR programme resulted in short-, medium- and long-term improvements in both physical and affective components of dyspnoea assessed by the D-12 questionnaire.

CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma.

BACKGROUND: One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment. RESEARCH QUESTION: What are the most relevant changes in CT scan parameters over time for assessing response to treatment? STUDY DESIGN AND METHODS: In this ancillary study of a randomized clinical trial (NEBULAMB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment. CT scans were assessed by two radiologists blinded to the clinical data. Radiologic parameters were determined by selecting those showing significant changes over time. Improvement of at least one, without worsening of the others, defined the radiologic response. Agreement between radiologic changes and clinical and immunologic responses was likewise investigated. RESULTS: Among the 139 originally randomized patients, 132 were included. We identified five CT scan parameters showing significant changes at end of treatment: mucoid impaction extent, mucoid impaction density, centrilobular micronodules, consolidation/ground-glass opacities, and bronchial wall thickening (P < .05). These changes were only weakly associated with one another, except for mucoid impaction extent and density. No agreement was observed between clinical, immunologic, and radiologic responses, assessed as an overall response, or considering each of the parameters (Cohen κ, -0.01 to 0.24). INTERPRETATION: Changes in extent and density of mucoid impaction, centrilobular micronodules, consolidation/ground-glass opacities, and thickening of the bronchial walls were found to be the most relevant CT scan parameters to assess radiologic response to treatment. A clinical, immunologic, and radiologic multidimensional approach should be adopted to assess outcomes, probably with a composite definition of response to treatment. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02273661; URL: www. CLINICALTRIALS: gov).

Frequency and characteristics of refractory dyspnea in idiopathic fibrosing interstitial pneumonia.

Patients with idiopathic fibrosing interstitial pneumonias (f-IIPs) mainly suffer from dyspnea. Refractory dyspnea, defined as persistent dyspnea despite optimal treatment, could be the signal to prescribe dyspnea relievers. We aimed to examine the prevalence and characteristics of refractory dyspnea in consecutive patients with f-IIPs. Refractory dyspnea was defined by an mMRC≥3 and also by a VAS dyspnea score≥2 at rest. The sensory and affective characteristics of refractory dyspnea (mMRC≥3) and associated quality of life (QoL) anxiety and depression were compared with non-refractory dyspnea (mMRC1-2) using the Multidimensional Dyspnea Profile (MDP), King's Brief Interstitial Lung Disease (KBILD) and Hospital Anxiety and Depression scale (HADs). We included 40 patients (24 men), aged 72 [68-79], FVC of 71 % [59-86] and DLCO 47 % [40-49]. Refractory dyspnea, was found in 38 % (95%CI:23-54) when defined by mMRC≥3 and in 67 % (95%CI:50-81) using a resting VAS dyspnea score ≥2. The agreement between the two definitions was low. Patients with refractory dyspnea (mMRC≥3) were more often women (60 % vs.28 %, p = 0.046), had a lower DLCO (24 % [22-43] vs.47 % [43-51], p = 0.014) and more frequently used oxygen (60 % vs.12 %, p = 0.003); they experience more intense air hunger (5/10 [3-6] vs.2/10 [0-5], p = 0.018)). No significant differences were observed in VAS, MDP, KBILD, or HADs scores between refractory and non-refractory dyspnea patients. Our results indicate a significant frequency of refractory dyspnea in patients with f-IIPs and an association with air hunger but no impact on the affective dimension of dyspnea, anxiety, depression and QoL, suggesting that the mMRC score might not accurately identify patients distressed by their breathlessness.

Continuous positive airway pressure compliance in patients with mild cognitive impairment.

PURPOSE: Sleep apnoea (SA) is associated with accelerated cognitive decline in patients with mild cognitive impairment (MCI). Treatment of SA by continuous positive airway pressure (CPAP) may slow this decline if patients comply with the treatment. The aim of this study was to assess the rate of CPAP compliance in this population. METHODS: In this single-centre retrospective study conducted in a tertiary care institution, patients with a diagnosis of MCI and SA initiating CPAP between January 2015 and August 2021 were included. Data from the initial sleep recording, the 3-month follow-up and compliance with at least 12 months of CPAP were analysed. Compliance was defined as an average CPAP use of at least 4 h per night. RESULTS: 55 patients were included (49% women, age 70.7 ± 8.9 years, body mass index 28.9 ± 6.5 kg/m2). Aetiology of MCI was vascular (45.5%), psychiatric (12.7%) and related to Alzheimer's disease (7.3%), with 47.3% of amnesic disorders and 45.5% of dysexecutive disorders. The MiniMentalState score was 26.7 ± 3.1. SA was mostly obstructive (81.8%) with a mean apnoea-hypopnoea index of 41.1 ± 16.4/h. At 3 months, 38 patients were compliant (69%) with a CPAP median use of 5.9 h per night and 83% of nights. Self-reported tolerance was better in compliant patients (75.7% vs 38.5% p = 0.017). Thirty-four patients remained compliant at 12 months (62%). CONCLUSION: Our results suggest a high rate of CPAP compliance in patients suffering from MCI. Compliance was related to the device tolerance, emphasizing the need to closely monitor and improve this factor.

Infections in autoimmune pulmonary alveolar proteinosis: a large retrospective cohort.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking. RESEARCH QUESTION: Describe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections. METHODS: We conducted a retrospective cohort including all patients diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected using a standardised questionnaire including demographics, comorbidities, imaging features, outcomes and microbiological data. RESULTS: We included 104 patients, 2/3 were men and median age at diagnosis was 45 years. With a median follow-up of 3.4 years (IQR 1.7-6.6 years), 60 patients (58%), developed at least one infection, including 23 (22%) with opportunistic infections. Nocardia spp was the main pathogen identified (n=10). Thirty-five (34%) patients were hospitalised due to infection. In univariate analysis, male gender was associated with opportunistic infections (p=0.04, OR=3.88; 95% CI (1.02 to 22.06)). Anti-granulocyte macrophage colony-stimulating factor antibody titre at diagnosis was significantly higher among patients who developed nocardiosis (1058 (316-1591) vs 580 (200-1190), p=0.01). Nine patients had died (9%), but only one death was related to infection. INTERPRETATION: Patients with aPAP often presented with opportunistic infections, especially nocardiosis, which highlights the importance of systematic search for slow-growing bacteria in bronchoalveolar lavage or whole lung lavage.

Home-based pulmonary rehabilitation for adults with severe asthma exposed to psychosocial chronic stressors.

OBJECTIVE: To evaluate the effects of a home-based pulmonary rehabilitation (PR) programme on hyperventilation symptoms, anxiety and depressive symptoms, general fatigue, health-related quality of life (HRQoL) and exercise capacity in adults with severe asthma who have been exposed to psychosocial chronic stressors. METHODS: Data on 111 non-selected consecutive adults with severe asthma who enrolled in an 8-week home-based PR programme (weekly supervised 90-min session) was retrospectively analysed. Chronic stressors included physical, sexual and psychological violence and/or a traumatic experience related to an intensive care unit stay. Hyperventilation symptoms (Nijmegen questionnaire), Hospital Anxiety and Depression Scale, Fatigue Assessment Scale, COPD Assessment Test, Six-Minute Stepper Test and Timed-Up and Go test were assessed at baseline and after PR. RESULTS: At baseline, participants who have been exposed to chronic stressors (n = 48, 43.2%) were younger, more often female, more often treated for anxiety and depressive disorders, and had a higher score for anxiety symptoms, hyperventilation symptoms and a poorer HRQoL, compared to those who had not been exposed to chronic stressors (p < 0.05). All the study assessments were statistically improved after PR for both groups (p < 0.001). Anxiety and depressive symptoms, fatigue and health-related quality of life questionnaires were also clinically improved based on the minimal clinically important difference. CONCLUSION: A large proportion of adults with severe asthma, mainly women, have been exposed to chronic stressors at the time of starting a PR programme, resulting in higher anxiety symptoms and hyperventilation symptoms. However, it did not prevent these individuals from benefiting from PR.

Pulmonary circulation abnormalities in post-acute COVID-19 syndrome: dual-energy CT angiographic findings in 79 patients.

OBJECTIVES: To evaluate the frequency and pattern of pulmonary vascular abnormalities in the year following COVID-19. METHODS: The study population included 79 patients remaining symptomatic more than 6 months after hospitalization for SARS-CoV-2 pneumonia who had been evaluated with dual-energy CT angiography. RESULTS: Morphologic images showed CT features of (a) acute (2/79; 2.5%) and focal chronic (4/79; 5%) PE; and (b) residual post COVID-19 lung infiltration (67/79; 85%). Lung perfusion was abnormal in 69 patients (87.4%). Perfusion abnormalities included (a) perfusion defects of 3 types: patchy defects (n = 60; 76%); areas of non-systematized hypoperfusion (n = 27; 34.2%); and/or PE-type defects (n = 14; 17.7%) seen with (2/14) and without (12/14) endoluminal filling defects; and (b) areas of increased perfusion in 59 patients (74.9%), superimposed on ground-glass opacities (58/59) and vascular tree-in-bud (5/59). PFTs were available in 10 patients with normal perfusion and in 55 patients with abnormal perfusion. The mean values of functional variables did not differ between the two subgroups with a trend toward lower DLCO in patients with abnormal perfusion (74.8 ± 16.7% vs 85.0 ± 8.1). CONCLUSION: Delayed follow-up showed CT features of acute and chronic PE but also two types of perfusion abnormalities suggestive of persistent hypercoagulability as well as unresolved/sequelae of microangiopathy. CLINICAL RELEVANCE STATEMENT: Despite dramatic resolution of lung abnormalities seen during the acute phase of the disease, acute pulmonary embolism and alterations at the level of lung microcirculation can be identified in patients remaining symptomatic in the year following COVID-19. KEY POINTS: • This study demonstrates newly developed proximal acute PE/thrombosis in the year following SARS-CoV-2 pneumonia. • Dual-energy CT lung perfusion identified perfusion defects and areas of increased iodine uptake abnormalities, suggestive of unresolved damage to lung microcirculation. • This study suggests a complementarity between HRCT and spectral imaging for proper understanding of post COVID-19 lung sequelae.

Allergic bronchopulmonary aspergillosis: A multidisciplinary review.

Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease characterized by a complex allergic inflammatory reaction of airways against Aspergillus affecting patients with chronic respiratory diseases (asthma, cystic fibrosis). Exacerbation is often the way to diagnose ABPA and marks its evolution by its recurrent character leading to cortico-requirement or long-term antifungal treatment. Early diagnosis allows treatment of ABPA at an initial stage, preventing recurrence of exacerbations and long-term complications, mainly represented by bronchiectasis. This review of the literature aims to present the current state of the art in terms of diagnosis and treatment of ABPA from a multidisciplinary perspective. As there is no clinical, biological nor radiological specific sign, diagnostic criteria are regularly revised. They are mainly based on the elevation of total and specific IgE against Aspergillus fumigatus and the presence of suggestive CT abnormalities such as mucoid impaction and consolidations. ABPA management includes eviction of mold and pharmacological therapy. Exacerbations are treated in first line with a moderate dose of oral corticosteroids. Azole antifungal agents represent an alternative for the treatment of exacerbations and are the preferential strategy to reduce the future risk of exacerbations and for corticosteroids sparing. Asthma biologics may be of interest; however, their place remains to be determined. Avoiding complications of ABPA while limiting the side effects of systemic drugs remains a major challenge of ABPA management. Several drugs, including new antifungals and asthma biologics, are currently being tested and may be useful in the future.

Severity and phenotypes of dyspnea in asthma: Impact of comorbidities.

BACKGROUND: Dyspnea is a common but non-specific symptom of asthma, which in particular may be related to anxiety and hyperventilation syndrome, two frequent comorbidities of asthma. METHODS: We conducted a prospective multicentric cohort study in dyspneic asthmatic adults. Dyspnea was assessed using the Multidimensional Dyspnea Profile questionnaire. We described the sensory (QS) and affective (A2) domains of dyspnea and investigated the effect of poor asthma control, hyperventilation and anxiety on each dimension at baseline and after 6 months. RESULTS: We included 142 patients (65.5% women, age: 52 years). Dyspnea was severe and predominated on its sensory domain (median QS: 27/50; A2: 15/50). Uncontrolled asthma (ACQ≥1.5), hyperventilation symptoms (Nijmegen≥23) and anxiety (HAD-A≥10) were present in 75%, 45.7% and 39% of cases, respectively. Hyperventilation symptoms were associated with higher QS and A2 scores: QS at 28.4(10.7) vs. 21.7(12.8) (p = 0.001) and A2 at 24(14) vs. 11.3(11) (p < 0.001) in patients with vs. without hyperventilation symptoms. Anxiety was only associated with increased A2 (27(12.3) vs. 10.9(11), p < 0.001). At 6 months, QS and A2 decreased of 7 and 3 points, respectively, in relation with changes in ACQ-6 and Nijmegen scores as well as the HAD-A score for A2. CONCLUSION: In breathless asthmatics, dyspnea is severe and worsened but differentially modulated by hyperventilation symptoms and anxiety. A multidimensional phenotyping of dyspnea in asthmatics could be useful to understand its origins and personalize treatment.

French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes.

Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES). Here, thanks to an extensive literature review, and thanks to the joint work of a large panel of experts involving physicians from both adult and pediatric medicine and from various subspecialties (as well as a representative of a patients' association representative), we provide recommendations for both the step-by step diagnostic workup of eosinophilia (whether unexplained or within specific contexts) as well as the management and follow-up of the full spectrum of eosinophilic disorders (including clonal, reactive, lymphocytic and idiopathic HES, as well as single-organ diseases). Didactic prescription summaries intended to facilitate the prescription of eosinophil-targeted drugs are also provided, as are practical diagnostic and therapeutic algorithms. Lastly, this set of recommendations also includes a summary intended for general practitioners, as well as an overview of the therapeutic patient education program set up by the French reference center for HES. Further updates will be mandatory as new validated information emerges.

Cross-sectional study to describe allergic rhinitis flare-ups and associated airways phenotype in house dust mite sensitization.

OBJECTIVES: To quantify and describe flare-ups of house dust mite allergic rhinitis (HDM-AR) which had occurred during the last 12 months in a population of adults and children candidate for Allergen ImmunoTherapy (AIT). Next, to identify associated clinical features. MATERIALS AND METHODS: This was an observational, multicenter, cross-sectional study that included patients aged ≥ 5 years with HDM-AR eligible for AIT and without prior AIT for at least 12 months. Flare-ups were all period with impairment of quality of life (QoL) and requiring a change in their usual treatment. Data were collected using medical records and patient questionnaires. Variables associated with the occurrence of ≥ 2 AR flare-ups were identified. RESULTS: 1,701 patients were included (average age: 23 years, 51.5% males, 30.4% children, 17.7% adolescents and 51.9% adults). Severe and persistent AR affected 70.9% of them and 53.7% showed polysensitization. Asthma was associated with AR in 34.4% and was well-controlled in 58.5%. The occurrence of at least one AR flare-up in the year was reported by 77.7%, with an annual rate in the whole population of 2.6 ± 3.9 and a duration of 14.1 ± 17.1 days. Deeply or moderately AR-related degraded QoL was experienced by 39.5% and 64.6%, respectively. The occurrence of ≥ 2 AR flare-ups was reported by 54.5% and was associated with polysensitization, AR intermittence and severity. CONCLUSION: AR flare-ups are frequent and impair QoL in HDM-allergic patients, suggesting that it could be considered as therapeutic targets.

Impact of Cardiovascular and Metabolic Comorbidities on Long-term Outcomes of Home-based Pulmonary Rehabilitation in COPD.

Background: Cardiovascular and metabolic comorbidities in chronic obstructive pulmonary disease (COPD) are associated with higher symptoms burden. Few center-based studies have evaluated the impact of these comorbidities on short-term pulmonary rehabilitation outcomes with contrasting results. Research Question: This study aimed to determine whether cardiovascular diseases and metabolic comorbidities impacted long-term outcomes of a home-based PR program in COPD patients. Study Design and methods: Data of 419 consecutive COPD patients addressed to our pulmonary rehabilitation program between January 2010 and June 2016 were retrospectively analyzed. Our program consisted of once-weekly supervised home sessions, including therapeutic education and self-management support, with unsupervised retraining exercises and physical activities the other days for 8 weeks. Exercise capacity (6-min stepper test [6MST]), quality of life (visual simplified respiratory questionnaire), and anxiety and depression (hospital anxiety and depression scale) were assessed respectively, before (M0) and at the end (M2) of the pulmonary rehabilitation program, and at 6 (M8) and 12 months (M14) after its achievement. Results: Patients (mean age 64.1±11.2 years, 67% males, mean forced expiratory volume in one second (FEV1) 39.2±17.0% predicted) were classified as having cardiovascular comorbidities (n=195), only metabolic disorders (n=122) or none of these comorbidities (n=102). After adjustment, all outcomes appeared similar between groups at baseline and improved after pulmonary rehabilitation with a greater effect at M14 for patients with only metabolic disorders on anxiety and depression score (-5.0±0.7 vs -2.9±0.8 and -2.6±0.6, p=0.021). Quality of life and exercise capacity improvements were not significantly different between the three groups at M2 and M14. Conclusion: Cardiovascular and metabolic comorbidities do not preclude COPD patients from obtaining clinically meaningful improvements in exercise capacity, quality of life and anxiety-depression up to 1 year after a home-based pulmonary rehabilitation.

French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis - 2021 update. Full-length version.

BACKGROUND: Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. METHODS: Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. RESULTS: After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.

High Frequency of Specific Polysaccharide Antibody Deficiency in Adults With Unexplained, Recurrent and/or Severe Infections With Encapsulated Bacteria.

BACKGROUND: Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD). METHODS: In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3). Main exclusion criteria were all local and general conditions that could explain infections. If no PID diagnosis was made, response to polysaccharide antigens was assessed using a pneumococcal polysaccharide vaccine. RESULTS: From March 2015 to March 2020, 118 patients were included (37 males, median age of 41 years): 73, 17, and 28 in groups 1, 2, and 3, respectively. Forty-seven PIDs were diagnosed, giving an estimated frequency of 39.8% (95% confidence interval [CI] [30.4, 48.8]). SPAD was the most frequent diagnosis by far (n = 37/47, 78.7%), and was made in 23, 5, and 9 patients from groups 1 to 3, respectively. All SPAD patients received conjugate vaccines and, according to their infectious history, were on surveillance or treated with preventive antibiotics (n = 6) and/or with immunoglobulins replacement therapy (n = 10), the latter being dramatically efficient in all cases. CONCLUSIONS: Considering its high prevalence among adults with unexplained recurrent and/or severe bacterial infections, SPAD should be screened in those patients. CLINICAL TRIALS REGISTRATION: NCT02972281.