The Efficacy of Omalizumab in Patients with Chronic Rhinosinusitis with Nasal Polyps and Comorbid Severe Allergic Asthma.

Chronic rhinosinusitis whit nasal polyps (CRSwNP) is the most common comorbid disease accompanying asthma. Omalizumab is a recombinant anti-immunoglobulin (Ig) E antibody, and studies suggest that omalizumab may also affect CRSwNP regardless of asthma. We aimed to assess the effect of omalizumab treatment on CRSwNP accompanying severe allergic asthma (SAA) patients. Clinical data including spirometry measurements, serum/nasal secretion biomarker levels were collected. NP scores and CRS scores (Lund-Mancay [LM] scores) were also recorded before omalizumab treatment, as well as at the 4th and 12th months of omalizumab treatment. Twenty-one patients with both CRSwNP and SAA who underwent omalizumab therapy were assessed. There was a significant difference among forced expiratory volume (FEV1), ACT scores, NP scores, LM scores, serum IgE, and blood eosinophil levels of the patients before omalizumab therapy at the 4th and 12th months of omalizumab treatment. A significant negative correlation was observed between ∆FEV1 and ∆NP scores (r=-0.485), between ∆ACT and ∆NP scores (r=-0.469), and ∆ACT and ∆LM scores (r=-0.436). When we grouped the patients who benefited from 1 year of omalizumab therapy and those who did not in terms of NP, there was no difference between the two groups related to local eosinophil and local IgE levels in the nasal polyp biopsy. Omalizumab treatment is effective for asthma and CRSwNP in patients with CRSwNP accompanied by SAA. Improvement in asthma is associated with improvement in CRSwNP. The efficacy of omalizumab on NP in patients with CRSwNP accompanied by SAA is independent of local IgE and eosinophil counts.

Evidence of the association between asthma and lung cancer risk from mendelian randomization analysis.

Asthma and lung cancer are both significant public health concerns worldwide. Previous observational studies have indicated a potential link between asthma and an increased risk of lung cancer, whereas the causal relationship remains uncertain. We aimed to investigate the potential causal relationship between asthma and lung cancer risk utilizing Mendelian randomization (MR) design.The present study employed a two-sample MR analysis utilizing summary statistics from genome-wide association studies (GWAS) with European descent of asthma and lung cancer. The MR analysis was performed using inverse variance weighting (IVW), supplemented with MR-Egger regression and weighted median method to investigate the potential causality between asthma and lung cancer. Furthermore, Sensitivity analyses were also conducted to ensure the reliability of the findings. The MR analysis showed that genetically predicted asthma had suggestive causal association with the elevated risk of lung cancer [odds ratio (OR), 1.05 (95%Cl,1.01-1.09), P = 0.01]. The consistent direction of effects observed in the three methods further supported this finding. In addition, sensitivity analyses demonstrated the reliability of the results. This study provided potential evidence supporting a causal association between asthma and lung cancer. These findings highlighted the importance of early detection and prevention strategies for lung cancer in individuals with asthma. Further research was needed to elucidate the underlying mechanisms linking asthma and lung cancer.

Efficacy of dupilumab on chronic rhinosinusitis with nasal polyps and concomitant asthma in biologic-naive and biologic-pretreated patients.

OBJECTIVES: Dupilumab, an anti-IL-4 receptor monoclonal antibody (mAb), was recently approved for the treatment of severe chronic rhinosinusitis with nasal polyps (CRSwNP). The main objective of this study was to assess whether previous exposure to biological treatment affected the clinical outcomes in CRSwNP and asthma patients, treated with dupilumab over time. A collateral secondary objective was to analyse the effects over time of dupilumab in patients with and without aeroallergen sensitization. METHODS: Single-centre retrospective observational study on severe CRSwNP patients treated with dupilumab. Nasal polyp score (NPS), visual analogue scale (VAS) symptom score, sinonasal outcome test (SNOT-22), aeroallergen sensitization, total serum IgE levels, and blood eosinophil counts were assessed at baseline and after 4, 6 and 12 months. RESULTS: 42 patients were included, 40 (95.2%) had asthma. Twenty-one (50%) patients received dupilumab without prior biological treatment (Group A: naive) and 50% switched to dupilumab from previous biological treatment (Group B: pre-treated). NPS, VAS symptoms, SNOT-22 improved significantly after 12 months treatment in both groups of patients (p < 0.001). After 12 months, VAS overall symptom score showed a significant reduction from 6 (IQR, 4.6-8.6) and 6 (IQR, 3.8-7.1) for Group A and Group B patients respectively, to 1.2 (IQR, 0.8-2.7) and 1.2 (IQR, 0.2-2.5); NPS from 6 (IQR, 4.0-7.0) and 5 (IQR, 3.5-6.0), respectively, to 1 (IQR, 0.0-2.0) and 0 (IQR, 0.0-3.0) and SNOT-22 from 64 (IQR, 56-78) and 71 (IQR, 47.5-76.0) respectively, to 5.5 (IQR, 4-21) and 6 (IQR, 4-15). IgE reduced from 57 to 22.1 and from 46.9 to 30.2 in Group A and Group B respectively (p < 0.001). CONCLUSIONS: Dupilumab improves symptom severity, polyp size, and health-related quality of life, regardless of the presence or absence of comorbid aeroallergen sensitization and previous administration of biologic therapy.

Dupilumab proved to be effective in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP).We observed that dupilumab for CRSwNP leads to a very rapid improvement in polyps, symptoms, and quality of life, regardless of previous biologic treatment status and presence or absence of allergic rhinitis.VAS, SNOT-22 and NPS may be established as outcome markers in everyday clinical practice during dupilumab treatment.

Improvement in health-related quality of life questionnaires with biologic treatment in severe asthma and comorbid chronic rhinosinusitis with or without nasal polyposis: a real-life experience.

BACKGROUND: Patients with severe asthma frequently have comorbid chronic rhinosinusitis (CRS) with or without nasal polyps, that can increase the symptom burden and complicate treatment. Real-life clinical data on the impact of biologic treatments on CRS-specific quality-of-life questionnaires are still lacking. MATERIALS AND METHODS: In this retrospective real-life study, we collected data from patients with severe asthma with comorbid CRS with/without nasal polyposis at baseline, and after 3, 6 and 12 months of treatment with omalizumab, mepolizumab, benralizumab or dupilumab. In particular, we evaluated improvements in HRQoL as measured by SinoNasal Outcome Test-22 (SNOT-22, 0 - 110), Visual Analog Scale symptom scores (VAS, 0-10), and Asthma Control Test (ACT, 5-25) and the proportion of patients meeting the minimal clinically important difference (MCID). RESULTS: Disease-specific HRQoL, as measured by SNOT 22 and VAS score improved in all patients at 3, 6, and 12 months of treatment compared with baseline (SNOT-22: 14, IQR: 0-52 vs 10, IQR:0-30 vs 0, IQR:0-15 vs 0, IQR:0-12, p < 0.001, VAS score: 1, IQR: 0-5 vs 0, IQR:0-3 vs 0, IQR:0-2 vs 0, IQR 0-1, p < 0.001). After 3 months of treatment >80% of patients reached the MCID for ACT, while only patients on dupilumab showed to reach a MCID in 100% of cases. The effect size depended upon the symptom burden at baseline. CONCLUSIONS: The study confirms the efficacy of omalizumab, mepolizumab, benralizumab, and dupilumab in a real-life setting, with a rapid improvement in CRS-specific HRQoL and general health status. These data highlight the importance of targeting type 2 inflammation in asthmatic patients with co-existing upper and lower airways disease.The Authors disclose that preliminary data and analysis of the present study have been presented in abstract form during the "X International Workshop on Lung Health - Respiratory Disease and Immune Response", held in Nice on 19-21 January 2023.

Sex Differences in Chronic Cough Epidemiology: The Korean Cough Study Group.

BACKGROUND: Chronic cough is a common symptom encountered by healthcare practitioners. The global prevalence of chronic cough is 9.6%, with a female predominance. The aim of our study is to reveal the sex differences in prevalence and severity of chronic cough in South Korea, stratified by age and etiology. METHODS: This study included adult patients with chronic cough who were recruited from 19 respiratory centers in South Korea. Patients completed the cough numeric rating scale (NRS) and COugh Assessment Test (COAT) questionnaire to assess the severity and multidimensional impact of cough. RESULTS: Among the 625 patients, 419 (67.0%) were females, with a male-to-female ratio of 1:2.03. The mean age was 49.4 years, and the median duration of cough was 12 weeks. The mean NRS and COAT scores were 5.5 ± 1.8 and 9.5 ± 3.6, respectively. Female patients were older (45.3 ± 15.4 vs. 51.6 ± 15.2, P < 0.001) and more likely to have asthma/cough variant asthma (CVA) (26.7% vs. 40.8%, P = 0.001) than male patients. There was no difference in the duration or severity of cough between sexes, regardless of the cause. The male-to-female ratio was lower for upper airway cough syndrome (UACS), asthma/CVA, and gastro-esophageal reflux disease (GERD), but not for eosinophilic bronchitis (EB) or unexplained cough. The mean age of female patients was higher in UACS and asthma/CVA, but not in EB, GERD, or unexplained cough. The majority (24.2%) fell within the age category of 50s. The proportion of females with cough increased with age, with a significant rise in the 50s, 60s, and 70-89 age groups. The severity of cough decreased in the 50s, 60s, and 70-89 age groups, with no significant sex differences within the same age group. CONCLUSION: The sex disparities in prevalence and severity of cough varied significantly depending on the age category and etiology. Understanding the specific sex-based difference could enhance comprehension of cough-related pathophysiology and treatment strategies.

Fatigue in severe pediatric asthma patients: Results of the PANDA study.

BACKGROUND: Fatigue is a commonly reported clinical symptom, yet research on fatigue in children with severe asthma is missing. We aimed to explore the extent of fatigue in severe pediatric asthma and identify associated factors. METHOD: This study was conducted within the Pediatric Asthma Non-Invasive Diagnostic Approaches (PANDA), an observational cohort of 6- to 17-year-old Dutch children with severe asthma. The Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL™-MFS) was used to measure self-reported fatigue. Fatigue levels were compared with a general pediatric Dutch population using linear regression, and quantifying the prevalence of "fatigued" (-2 < Standard deviations [SD] ≤ -1) and "severely fatigued" (SD ≤ -2) children. Secondly, we performed linear regression analyses to explore whether fatigue levels were independently associated with asthma attacks, comorbidities, medication, pulmonary function, symptom control, and asthma-related quality of life (QoL). RESULTS: Severe pediatric asthma patients (n = 78, mean age 11.8 ± 3.1 years) reported significantly more fatigue than Dutch peers (n = 328, mean age 11.8 ± 3.2 years) mean difference in z-score: -0.68; 95%CI -0.96, -0.40. In the severe asthma group, 28.2% scored as "fatigued" and 15.4% as "severely fatigued," compared with 14.0% and 3.4% in the general population. In pediatric asthma patients, asthma-related QoL (ß = 0.77, p < .01, ΔR2 = .43), symptom control (ß = 0.56, p < .01, ΔR2 = .24) and a dysfunctional breathing pattern (ß = -0.36, p < .01, ΔR2 = .12) were most strongly associated with fatigue scores. CONCLUSION: Fatigue is a common symptom in children with severe asthma and is associated with multiple clinical factors and patient-reported outcomes. It should be considered as an important treatment target.

Curcumin Alleviates Airway Inflammation in Cough-Variant Asthmatic Rats by Modulating M1/M2 Macrophage Polarization.

BACKGROUND: With the increase of environmental pollution and atypical pathogen infections, the incidence of cough variant asthma (CVA) has been increasing annually, making it a pressing issue of the medical community. This study aims to observe the ameliorative effect of curcumin on a rat model of cough variant asthma. METHODS: A rat model of cough variant asthma was induced by sensitization with ovalbumin combined with aluminum hydroxide (Al(OH)3), followed by repeated excitations. The drug was administered on the day of the initial nebulized attack, and gavage was administered for 14 d. Pathological changes in the lung tissues were observed, along with the assessment of cough susceptibility and airway resistance. The number of inflammatory cell eosinophils and leukocytes were determined in alveolar lavage fluid. Additionally, serum inflammatory factors and lung tissues Matrix Metalloproteinase-9 (MMP-9) protein were assessed. The level of M1/M2 macrophages was also detected. RESULTS: Following the administration of curcumin, there was reduced inflammatory infiltration, less disordered arrangement of the lung tissue, and decreased abnormal proliferation of lung tissues in cough variant asthma rats compared to the model group. Curcumin treatment led toa notable reduction in cough frequency, a significant decrease in pro-inflammatory factor concentration levels in serum and inflammatory cell counts in the alveolar lavage fluid, and a marked increase in anti-inflammatory factor levels (p < 0.05). Additionally, curcumin administration led to a significant increase in M2-type macrophage levels, while simultaneously decreasing the levels of M1-type macrophages (p < 0.05). CONCLUSIONS: The administration of curcumin effectively ameliorates ovalbumin-induced airway inflammation in cough-variant asthma rats. This effect is attributed to modulating macrophage polarization towards the anti-inflammatory M2 phenotype, thereby reducing airway inflammation, airway hyperresponsiveness, and lung tissue injury.

Association between Frailty and Asthma.

Background and Objectives: This study investigated whether there is an association between elderly frailty and asthma. Material Methods: We examined 9745 elderly participants who did not have asthma and 275 elderly patients who had asthma diagnosed by a doctor from the 2020 Survey of Living Conditions and Welfare Needs of Korean Older Persons Survey. Study Selections: The Korean version of the fatigue, resistance, ambulation, illnesses, and loss of weight (K-FRAIL) scale was used to determine their level of frailty. The relationship between frailty and geriatric asthma was examined using multiple logistic regression analysis, which was adjusted for a number of confounding variables (socioeconomic, health behavior, psychological characteristics, and functional status). Results: Frailty as defined by the K-FRAIL scale was significantly higher in the asthma group (7.6%) than the non-asthma group (4.9%). The frailty phenotype component showed that resistance, ambulation, and illness severity were more severe in the asthma group than the non-asthma group. After adjusting, asthma was significantly associated with an increased risk of frailty (OR 1.45; 95% confidence interval [CI] 1.01-2.09) compared to the non-asthma group. Conclusions: Frailty might be associated with elderly asthma in patients from the Korean population. Frailty may not only be associated with asthma, but also with other diseases. So, more evidence is needed to establish this association.

Congenital Long QT Syndrome Unmasked by Albuterol in an Adolescent with Asthma.

BACKGROUND: Patients with congenital long QT syndrome (LQTS) are prone to ventricular dysrhythmia but may be initially asymptomatic with a normal QTc interval on resting electrocardiogram (ECG). Albuterol is listed as a medication that poses a "special risk" to patients with congenital LQTS, but its effects have been rarely described. We present a case of previously unknown, asymptomatic congenital LQTS unmasked by albuterol in an adolescent with asthma. CASE REPORT: A 12-year-old girl with a history of asthma presented to the emergency department (ED) with shortness of breath, wheezing, and tachycardia for 24 h, consistent with acute asthma exacerbation. She received two doses of her home albuterol inhaler 2 h prior to presentation. Initial ECG demonstrated a QTc of 619 ms. Her remaining history, clinical examination, and laboratory workup, including electrolytes, were unremarkable. She was observed with cardiac monitoring before being discharged from the ED in stable condition for next-day outpatient pediatric cardiology follow-up. Resting office ECGs revealed QTcs from 440-470 ms. Exercise stress test revealed QTc prolongation of 520 ms and 500 ms at minute-2 and minute-4 of recovery, respectively. Genetic testing revealed heterozygous pathogenic variants in KCNQ1, consistent with type 1 LQTS. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Albuterol may be a cause of marked QTc prolongation in ED patients with underlying congenital LQTS, which can be a diagnostic clue in previously unidentified patients. Extreme QTc prolongation also serves as an indication in the ED for Cardiology consultation, laboratory evaluation for electrolyte imbalances, and observation with cardiac monitoring.

Asthma and health-related quality of life at 16-20 years of age in a prospectively followed post-bronchiolitis cohort.

The aim was to evaluate asthma and health-related quality of life (HRQoL) outcomes in adolescents, after hospital-treated bronchiolitis experienced in less than 6 months of age. A prospective cohort study started in 2001-2004 and followed up 166 children hospitalised for bronchiolitis in early infancy. At 16-20 years of age, 76 cases and 41 population-based controls without a history of bronchiolitis participated in the current study. Clinical asthma, presumptive symptoms and HRQoL data were collected with a structured questionnaire and the St. Georges Respiratory Questionnaire (SGRQ). Flow-volume spirometry was measured before and after bronchodilator administration. Asthma was present in 21.1% of cases in the post-bronchiolitis cohort compared to 9.8% in the control group (p = 0.21). Also, 35.5% of cases and 19.5% of controls reported dyspnea during the last 12 months (p = 0.04). In addition, total SGRQ scores were higher in the bronchiolitis group (4.26) than in the control group (1.67, p < 0.001) referring to a reduced health-related quality of life. CONCLUSION: Viral bronchiolitis in early infancy was associated with increased respiratory symptoms and lower health-related quality of life at age 16-20 years. WHAT IS KNOWN: • The prevalence of asthma at the school age and adolescence is increased after hospitalisation required bronchiolitis in infancy compared to those without hospitalisation due to bronchiolitis. WHAT IS NEW: • Viral bronchiolitis requiring hospitalisation in early infancy was associated with increased respiratory symptoms, such as dyspnoea, and lower health-related quality of life at age 16-20 years in a prospectively followed post-bronchiolitis cohort.

New-onset obstructive airway disease following COVID-19: a multicenter retrospective cohort study.

BACKGROUND: The study assessed the association between COVID-19 and new-onset obstructive airway diseases, including asthma, chronic obstructive pulmonary disease, and bronchiectasis among vaccinated individuals recovering from COVID-19 during the Omicron wave. METHODS: This multicenter retrospective cohort study comprised 549,606 individuals from the U.S. Collaborative Network of TriNetX database, from January 8, 2022, to January 17, 2024. The hazard of new-onset obstructive airway diseases between COVID-19 and no-COVID-19 groups were compared following propensity score matching using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: After propensity score matching, each group contained 274,803 participants. Patients with COVID-19 exhibited a higher risk of developing new-onset asthma than that of individuals without COVID-19 (adjusted hazard ratio (aHR), 1.27; 95% CI, 1.22-1.33; p < 0.001). Stratified analyses by age, SARS-CoV-2 variant, vaccination status, and infection status consistently supported this association. Non-hospitalized individuals with COVID-19 demonstrated a higher risk of new-onset asthma (aHR, 1.27; 95% CI, 1.22-1.33; p < 0.001); however, no significant differences were observed in hospitalized and critically ill groups. The study also identified an increased risk of subsequent bronchiectasis following COVID-19 (aHR, 1.30; 95% CI, 1.13-1.50; p < 0.001). In contrast, there was no significant difference in the hazard of chronic obstructive pulmonary disease between the groups (aHR, 1.00; 95% CI, 0.95-1.06; p = 0.994). CONCLUSION: This study offers convincing evidence of the association between COVID-19 and the subsequent onset of asthma and bronchiectasis. It underscores the need for a multidisciplinary approach to post-COVID-19 care, with a particular focus on respiratory health.

Infectious acute respiratory failure in patients under 5 years of age: a retrospective cohort study.

BACKGROUND: Acute lower respiratory infections in children under 5 years present a real challenge for diagnosis and treatment and are the first cause of mortality for this group of age. The study aimed to describe the characteristics of infectious acute respiratory failure due to bronchiolitis, pulmonary infection or severe acute asthma related to a virus or bacteria in this population of children under 5 years old at admission to the paediatric intensive care unit (PICU), PICU management and outcomes in order to better identify the needs of these patients. Our secondary aim was to compare the characteristics and PICU management of this population (1) depending on their age (less or more than 6 months old) and (2) depending on the pulmonary imaging (absence or presence of an alveolar condensation on the chest X-ray or lung ultrasound). METHODS: We conducted a retrospective study in two PICUs in the Ile-de-France region. We included children under 5 years old hospitalised between 1 January 2017 and 31 December 2021 due to a respiratory infection complicated by acute respiratory failure. RESULTS: We included 707 patients. The median age was 3 months. On arrival, patients were oxygen-dependent with a mean fraction of inspired oxygen (FiO2) of 34% and 63% required non-invasive ventilation (NIV). During hospitalisation, more than 70% required ventilatory support by NIV and 10% by tracheal intubation. 18% required volaemic expansion and 4% vasopressors. Nearly 90% of PCRs for respiratory viruses were positive, and respiratory syncytial virus (RSV) was found in almost two-thirds of cases. Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were frequently found. Significantly, patients aged less than 6 months old needed more NIV, had less alveolar condensation, had slightly lower oxygen requirements, a less frank inflammatory syndrome and a more frequently positive PCR for respiratory viruses. CONCLUSIONS: We highlighted similarities between patients hospitalised for lower respiratory infection in PICU in France and those in Australia or Brazil. Optimal management relies mainly on NIV, oxygen therapy with FiO2 under 40% and available antibiotics. These results lead us to believe that the implementation of NIV training and equipment could help reduce mortality due to lower respiratory infections in children worldwide.

Is using inhaled corticosteroid effective against COVID-19 pneumonia severity and mortality?

Introduction: It is known that the use of inhaled corticosteroids increases the incidence of pneumonia in patients followed up with the diagnosis of chronic asthma and chronic obstructive pulmonary disease (COPD). This study aimed to investigate the contribution of inhaled steroid use to pneumonia severity and mortality in cases with COVID-19 pneumonia. Materials and Methods: The study is a retrospective, observational study. Among the cases admitted to the pandemic clinic, patients diagnosed with COVID-19 pneumonia were included. The plan was to compare cases who received and did not receive inhaled corticosteroids in terms of pneumonia severity and mortality. In order to define risk factors for mortality, univariate and multivariable negative binomial regression analyses were performed. Result: In our study, it was observed that n= 540 (75%) cases did not receive inhaled corticosteroids (group 1), and 180 (25%) cases used inhaled corti costeroids (group 2). Group 1 and group 2 cases were compared in terms of pneumonia severity with no significant difference between the two groups (p= 0.11). Then, risk factors affecting mortality in all cases were examined with univariate analyses. Increasing age, applying mechanical ventilation, having severe pneumonia, having interstitial lung disease, and applying prone position were found to be statistically significant factors in mortality (p < 0.05). Conclusions: In conclusion, in our study, it was observed that the use of inhaled corticosteroids did not increase the severity of pneumonia and mortality. It was thought that the treatment they received could be continued when the patients treated with inhaled corticosteroids due to asthma and COPD had COVID-19 pneumonia.

Differences in the Quantitative HRCT Characteristics of Patients with Asthma, COPD and Asthma-COPD Overlap and Their Relationships with Pulmonary Function.

Purpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma-COPD overlap (ACO) and explored their relationships with airflow limitation. Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of -860 HU to -950 HU (RVC-860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structure‒function relationships. Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC-860 to -950 levels decreased in the following order: ACO, COPD, and asthma. RVC-860 to -950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC-860 to -950 in ACO patients. Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.

Development and validation of a novel questionnaire to describe and assess sensations and triggers associated with refractory and unexplained chronic cough.

INTRODUCTION: Refractory or unexplained chronic cough (RUCC) is a common clinical problem with no effective diagnostic tools. The Sensations and Triggers Provoking Cough questionnaire (TOPIC) was developed to characterise cough in RUCC versus cough in other conditions. METHODS: Content analysis of participant interviews discussing the sensations and triggers of chronic cough informed TOPIC development. Participants with chronic cough completed the draft-TOPIC (a subset repeating 5-7 days later), St George's Respiratory Questionnaire (SGRQ), Cough Severity Diary (CSD) and Global Rating of Change Scale. The draft-TOPIC item list was reduced in hierarchical and Rasch analysis to refine the questionnaire to the TOPIC. RESULTS: 49 items describing the triggers and sensations of cough were generated from participant interviews (RUCC n=14, chronic obstructive pulmonary disease (COPD) n=11, interstitial lung disease (ILD) n=10, asthma n=11, bronchiectasis n=3, cystic fibrosis n=7). 140 participants (median age 60.0 (19.0-88.0), female 56.4%; RUCC n=39, ILD n=38, asthma n=45, COPD n=6, bronchiectasis n=12) completed draft-TOPIC, where items with poor 'fit' for RUCC were removed to create TOPIC (8 trigger items, 7 sensation items). Median TOPIC score was significantly higher in RUCC (37.0) vs ILD (24.5, p=0.009) and asthma (7.0, p<0.001), but not bronchiectasis (20.0, p=0.318) or COPD (18.5, p=0.238), likely due to small sample sizes. The Rasch model demonstrated excellent fit in RUCC (χ2=22.04, p=0.85; PSI=0.88); as expected. When all participant groups were included, fit was no longer demonstrated (χ2=66.43, p=0.0001, PSI=0.89) due to the increased heterogeneity (CI=0.077). TOPIC correlated positively with SGRQ (r=0.47, p<0.001) and CSD (r=0.63, p<0.001). The test-retest reliability of TOPIC (intraclass correlation coefficient) was excellent (r=0.90, p<0.001). CONCLUSIONS: High TOPIC scores in the RUCC patients suggest their cough is characterised by specific sensations and triggers. Validation of TOPIC in cough clinics may demonstrate value as an aid to identify features of RUCC versus cough in other conditions.

Exploring the Relationship between Inhaled Corticosteroid Usage, Asthma Severity, and Sleep-Disordered Breathing: A Systematic Literature Review.

(1) Background: Sleep-disordered breathing and asthma are often interrelated. Children and adults with asthma are more susceptible to sleep apnea. Inhaled corticosteroids effectively reduce inflammation and prevent structural changes in the airways. Objective: to explore the existing literature to determine whether inhaled corticosteroids play a role in sleep-disordered breathing in patients with asthma. (2) Methods: We conducted a thorough search of the PubMed, Scopus, and Web of Science databases for English-language articles published up to 12 May 2024. We utilized the ROBINS-E tool to assess the risk of bias. (4) Conclusions: 136 articles were discerned upon conducting the literature search. A total of 13 articles underwent exhaustive full-text scrutiny, resulting in 6 being considered non-relevant. The remaining seven articles, assessed for eligibility, were incorporated into the final analysis. Five studies were identified in adults and two in children. In adult patients, inhaled corticosteroids, especially at high doses, appear to increase the risk of sleep apnea in a dose-dependent manner. Moreover, the properties of inhaled corticosteroids, such as particle size, may impact the risk of developing sleep apnea. In children, the severity of asthma is a key factor affecting the prevalence of sleep apnea, whereas inhaled corticosteroids appear to be a less significant risk factor compared to adults. All of the studies reviewed were classified as having a high risk of bias or some concerns regarding bias. Each study revealed at least one type of bias that raised notable concerns. This research highlights a complex interaction between the use of inhaled corticosteroids, the severity of asthma, and the onset of sleep apnea. Additional research is necessary to investigate these relationships further.