Correlation analysis of serum Rac1 level with asthma control, airway inflammatory response and lung function in asthmatic children.

OBJECTIVE: To investigate the correlation between serum Rac1 enzyme (Rac1) level with asthma control, airway inflammatory response and lung function in asthmatic children. METHODS: A retrospective analysis was performed on 79 children with asthma who were diagnosed and treated in our hospital from June 2020 to January 2023. According to the severity of the disease, the children were divided into mild group (25 cases), moderate group (30 cases) and severe group (24 cases). 36 healthy children who underwent physical examination at the same period in our hospital were selected as the control group. The state of an illness, control level, serum mRNA Rac1, inflammatory factors, and lung function of the children in two groups were compared between the control group and the observation group. RESULTS: The Rac1 mRNA levels, forced vital capacity (FVC), forced expiratory volume in one second/FVC (FEV1/FVC), peak expiratory flow (PEF), and maximum mid-expiratory flow (MMEF) in the observation group were significantly lower than these in the control group (P < 0.05). The tumor necrosis factor-alpha (TNF-α), interleukin-5 (IL-5), IL-6, and IL-33 in the observation group were markedly higher than these in the control group (P < 0.05). As the state of an illness worsened, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually reduced (P < 0.05), while the levels of TNF-α, IL-5, IL-6, and IL-33 increased (P < 0.05). As the degree of disease control improved, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually elevated (P < 0.05), and the levels of TNF- α, IL-5, IL-6, and IL-33 showed the opposite trend (P < 0.05). Rac1 was negatively related to the levels of TNF-α, IL-5, IL-6 and IL-33 (P < 0.05), and positively to the levels of FVC, FEV1/FVC, PEF and MMEF (P < 0.001). Rac1 mRNA levels, FVC, FEV1/FVC, PEF and MMEF were protective factors, while TNF-α, IL-5, IL-6 and IL-33 were risk factors for the prognosis of children with asthma (P < 0.05). CONCLUSION: Children with asthma have obviously lower serum Rac1 mRNA levels, higher inflammatory factor levels and lower lung function. Serum Rac1 mRNA level may be associated with better asthma control, lower airway inflammatory response, better lung function and lower disease severity. It has important reference value for the evaluation of the state of an illness, efficacy and prognosis of children with bronchial asthma.

Effect of Small Doses of Azithromycin on Pulmonary Ventilation Function and Inflammatory Factors IL-6, IL-13 in Children with Bronchial Asthma.

OBJECTIVE: To observe the effect of low-dose azithromycin on pulmonary ventilation function and inflammatory factors IL-6, IL-13 in children with bronchial asthma. METHODS: A total of 80 children with asthma in Pediatric Medicine affiliated to Taizhou Women and Children's Hospital of Wenzhou Medical University from January 2019 to December 2022 were selected and divided into control group (42 cases) and study group (38 cases). The control group regularly inhaled Salmeterol Xinafoate and Fluticasone Propionate inhalation, while the study group was additionally given low-dose azithromycin. After four weeks of treatment, pulmonary function tests including FEV1, FVC were performed and inflammatory indicators including CRP, FeNO, IL-6, IL-13 were measured. The occurrence of adverse reactions during treatment was recorded. RESULTS: Pulmonary function tests including FEV1%, FEV1/FVC% were improved in all subjects, and the improvement of pulmonary function was more significant in the study group (P<0.05). The levels of CRP, FeNO, IL-6 and IL-13 were decreased in the two groups, especially in the study group (P<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (P>0.05). CONCLUSION: Low-dose azithromycin can significantly improve the pulmonary function in children with bronchial asthma, reduce the levels of inflammatory factors, control airway mucus secretion and inflammation, and can be used to treat chronic lung diseases such as bronchial asthma.

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.

Exhaled volatile organic compounds (VOCs) for prediction of asthma exacerbation in children.

OBJECTIVES: To find possible relationship between asthma exacerbation and metabolomic profile of airways, assessed by non-invasive method - free volatile organic compounds (VOCs) in exhaled air in children. MATERIAL AND METHODS: The study included 80 children aged 4-18 years with asthma: 42 children with a min. 3 asthma exacerbations in the past 12 months, and 38 children without a history of exacerbations in the past year. During the study visit, each patient was examined, medical history (including information regarding atopy and eosinophil blood count) was taken, spirometry and fractional exhaled nitric oxide (FeNO) were tested, an exhaled air sample was taken to test for the presence of VOCs, and the patient also completed standardized form - Asthma Control Questionnaire. Volatile organic compounds were measured by combined gas chromatography coupled to mass spectrometry. RESULTS: The obtained results of VOCs were correlated with the history of the disease. The 2 gas profiles were defined and they formed 2 clinically distinct clusters (p = 0.085). Cluster 2 was characterized for children with a higher number of bronchial asthma exacerbations and worse lung function parameters (predicted percentage forced expiratory volume in 1 s [FEV1] [p = 0.023], FEV1/ forced vital capacity ratio [FVC] [p = 0.0219]). The results were independent of the age, sex, BMI, atopy (house dust mite allergy) and eosinophil blood count. CONCLUSIONS: The study findings suggest that a relative group of gases may be a useful predictor of having asthma exacerbations in children. Additionally, a single FeNO value was unlikely to be clinically useful in predicting asthma exacerbations in children. The VOCs profile reflecting the metabolism of the airway epithelium and local microbiota was associated with the course of asthma, which strongly justifies further prospective validation studies. Int J Occup Med Environ Health. 2024;37(3):351-59.

Small airways response to bronchodilators as the marker of the uncontrolled asthma in children.

OBJECTIVE: Aim: To develop the criteria of small airways response to bronchodilators (by spirometry indices maximal expiratory flow (MEF50 and MEF25) as the markers of uncontrolled asthma course. PATIENTS AND METHODS: Materials and Methods: The study involved 92 participants (64 boys and 28 girls) aged 6 to 17 years (60 were less than 12 years old) with diagnosed asthma. Asthma control was assessed with the use of Asthma Control Test and Asthma Control Questionnaire. Spirometry and bronchodilator responsiveness testing were performed for all participants. RESULTS: Results: Mostly, the studied children had a normal level of forced expiratory volume in the first second (FEV1), even at unsatisfactory symptoms control. The indicators of the medium and small airways patency were significantly worse in uncontrolled asthma children even in normal FEV1. Among children, the lack of asthma control can be caused by small airways obstruction in up to 80% cases. Among children who need the high dose inhaled corticosteroids treatment 93.3% have uncontrolled asthma with small airways obstruction. We found out that MEF50 and MEF25 could be the signs of the reversibility of bronchial obstruction and uncontrolled asthma with high sensitivity and specificity. CONCLUSION: Conclusions: Indices MEF50 and MEF25 allow detecting the small airways obstruction and their reversibility as a mark of uncontrolled asthma (MEF25 has a higher diagnostic value). In case of MEF50 and/or MEF25 increasing for 22% or 25% accordingly in bronchodilator test in children, the asthma should be considered uncontrolled.

Comparative analysis of central aortic blood pressure, pulse wave velocity & arterial stiffness in patients with obstructive airway disease.

BACKGROUND: As the pulmonary system and cardiovascular system are intimately linked, patients with chronic obstructive pulmonary disease (COPD) and asthma have high risk for developing cardiovascular diseases (CVDs) and altered central hemodynamic. OBJECTIVE: We aim to assess the central aortic blood pressure (CABP) indices, pulse wave velocity (PWV) and other indicators of arterial stiffness in Indian patients with COPD and bronchial asthma. METHODS: This is a single-center, cross-sectional study conducted in outpatients diagnosed with either chronic stable phase of COPD or bronchial asthma. CABP indices, vascular age, arterial stiffness and central hemodynamics were measured in patients. RESULTS: Of 193 patients with obstructive airway disease who were enrolled, (n = 81 had COPD and n = 112 had partially-controlled bronchial asthma) the proportion of male patients was higher in both groups. The PWV, augmentation index (AI) and vascular age (VA) were significantly higher in patients with COPD compared to those with bronchial asthma (all, p < 0.05). CONCLUSION: The study showed that PWV, AI and VA were higher in patients with stable COPD without any cardiac comorbidities compared to bronchial asthma.

Clinical applications of forced oscillation technique (FOT) for diagnosis and management of obstructive lung diseases in children.

Obstructive lung diseases such as bronchial asthma, COPD, and cystic fibrosis are a burden on many patients across the globe. Spirometry is considered the gold standard for diagnosing airflow obstruction, but it can be difficult for pediatric patients to do and requires a lot of effort. As a result, healthcare providers need new, effortless methods to diagnose airway obstructions, particularly in young children and individuals unable to perform the spirometry maneuver. The forced oscillation technique is a modern method requiring only tidal breathing combined with the application of external, source of low-amplitude oscillations to evaluate the respiratory system's response. It might be essential for identifying early respiratory changes caused by smoking, childhood asthma, and may prove more sensitive than spirometry in identifying peripheral airway disturbances or evaluating the long-term success of therapy. This review describes the methodology and the indications for the forced oscillation technique and outlines its relevance in clinical practice.

Bronchial thermoplasty for severe asthma: potential mechanisms and response markers.

Severe asthma (SA) poses a significant challenge to management and treatment, leading to a reduced quality of life and a heavy burden on society and healthcare resources. Bronchial thermoplasty (BT) has emerged as a non-pharmacological intervention for SA, demonstrating its efficacy and safety in improving patients' quality of life and reducing exacerbation rates for over a decade. In particular, BT encounters various obstacles in its clinical application. Since asthma is characterized by high heterogeneity, not all patients derive effective outcomes from BT. Furthermore, current knowledge of markers that indicate response to BT remains limited. Recent research has shed light on the intricate mechanism of action of BT, which extends beyond simple smooth muscle ablation. Therefore, to enhance the clinical practice and implementation of BT, this paper aims to elucidate the mechanism of action and identify potential markers associated with BT response.

A review of a non-drug treatment for asthma to better understand the potential mechanisms and markers of the treatmentA non-drug treatment for asthma: Severe asthma leads to a low quality of life and places a heavy burden on society and healthcare resources. A non-drug treatment for asthma called bronchial thermoplasty is a technique that uses high temperatures to remove excess airway muscle. Its efficacy and safety in improving asthma patients' quality of life have been demonstrated for more than a decade. Barriers to the treatment development: When it comes to clinical application, bronchial thermoplasty faces several barriers. Asthma is characterized by high variability, and not all patients have good outcomes from bronchial thermoplasty. Understanding of the effectiveness of bronchial thermoplasty remains limited. New insights into how the treatment works: Recent research has found that the effect of bronchial thermoplasty is complicated and goes beyond simple muscle removal. What is the aim of this review: To improve the use of bronchial thermoplasty by discussing its effects on the body and identifying ways to measure how effective the treatment is.

[Severe asthma: Pathophysiology, diagnosis, and treatment]. / Asma grave: fisiopatología, diagnóstico y tratamiento.

Severe asthma is an entity with a complex diagnosis, requiring an adequate differential diagnosis and identification of endotypes for a correct approach and therapeutic process. In the present review, we show a synthesis of the current literature on the diagnosis, pathophysiology, and management of severe asthma, having critically analyzed the evidence in search engines such as Medline, Scopus, and Embase.

El asma grave es una enfermedad compleja, que requiere un enfoque y diagnóstico diferencial ordenado e identificación de endotipos para el correcto abordaje y tratamiento. El tratamiento farmacológico cuenta cada vez con más moléculas a disposición del personal médico para el control efectivo de los síntomas. Esta revisión muestra una síntesis de la bibliografía actual acerca del diagnóstico, fisiopatología y tratamiento del asma grave, mediante la lectura crítica previa de la evidencia científica en buscadores como Medline, Scopus y Embase.

[Clinical characteristics analysis of persistent airflow limitation in asthmatic children].

Objective: To analyze the clinical characteristics of asthmatic children with persistent airflow limitation (PAL) in order to improve understanding of PAL and improve asthma management. Methods: The clinic data of asthmatic children aged 6 to 18 years with and without PAL, who visited the Department of Allergy at Children's Hospital of the Capital Institute of Pediatrics between January 2021 and June 2023, were analyzed retrospectively. The study included a total of 197 patients (153 males and 44 females), with a median age of 9.0 (7.0, 12.0) years. The analysis encompassed demographic features, disease-related factors, laboratory tests, and spirometry parameters. Quantitative data differences between the two groups were assessed using the Student's t-test or the Mann-Whitney U test. Qualitative data comparisons were made using the Chi-square test or Fisher's exact test. Results: This study included 100 non-PAL and 97 PAL patients. The female-to-male ratio in the two groups was 27/73 and 17/80, respectively. Age and BMI were 11.0 (10.0, 13.0) years and 20.3 (17.7, 24.1) kg/m2 in the PAL group, which was significantly higher than in the non-PAL group (P<0.001). Among the PAL group, 49.5% fell within the 9-12 age group. The PAL group had a higher percentage of patients with an asthma duration of more than 3 years (89.7% vs. 62.0%, P<0.001) and a history of pneumonia (13.4% vs. 4.0%, P=0.036) compared to the non-PAL group. Regarding laboratory tests, a higher percentage of patients in the PAL group had an elevated FeNO level (60.9% vs. 37.6%, P=0.002) and animal sensitization (50.7% vs. 30.7%, P=0.022) compared to the non-PAL group. Of the 69 patients who underwent spirometry before and after PAL development, FEV1%pred, FEV1/FVC, and MMEF%pred values gradually decreased, with a significant decline in the year preceding PAL development. Conclusions: Asthmatic children with PAL had characteristics such as relatively older age, higher BMI, longer duration of asthma, eosinophilic inflammation, and atopy. Lung function decline occurred several years before PAL development. Long-term follow-up should focus on the evolving trend of spirometry parameters.

The prevalence of asthma and its predictor among patients presetting in Ethiopian public hospitals: systematic review and meta-analysis, 2024.

BACKGROUND: Asthma is a leading cause of emergency hospital visits and a significant factor in lost productive hours. The lack of a synthesized body of knowledge on bronchial asthma has notable public health implications. OBJECTIVE: This systematic review and meta-analysis aim to investigate the prevalence of asthma and its predictors among patients presenting in Ethiopian public hospitals. DESIGN: Duplicate studies were removed using EndNote version X9. The Newcastle-Ottawa Scale guided the quality assessment, and data extraction followed the Joanna Briggs Institute format. DATA SOURCE AND METHODS: The authors used advanced search methods, including databases such as PubMed, Scopus, Embase, Africa Index Medicus, Science Direct, HINARI, Google Scholar, and manual searches. Data presentation adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Publication bias was assessed using Egger's regression test and a funnel plot. Sensitivity analysis was also conducted. RESULTS: The search yielded 352 original articles, with 22 meeting the criteria for inclusion. Using the random-effects DerSimonian-Laird model, the prevalence of bronchial asthma was found to be 9.02% (95% CI: 7.50, 10.53). Several factors were associated with the prevalence of bronchial asthma, including the spring season (AOR 3.7; 95% CI: 2.11, 6.49), childhood age (AOR 4.2; 95% CI: 1.84, 9.55), and urban residence (AOR 1.7; 95% CI: 1.29, 2.31). Other significant factors include family history of asthma (AOR 2.89; 95% CI: 2.22, 3.75), insecticide exposure (AOR 3.3; 95% CI: 2.23, 4.91), and the presence of household insects like cockroaches (AOR 3.33; 95% CI: 2.15, 5.15). Smoking (AOR 3.64; 95% CI: 2.66, 4.98), obstructive sleep apnea (AOR 4.29; 95% CI: 2.37, 7.76), and recurrent upper respiratory tract infections (AOR 4.31; 95% CI: 2.24, 8.32) were also significant. CONCLUSION: The pooled prevalence of bronchial asthma is notably high in Ethiopia. Key predictors include childhood age, spring season, urban living, family history of asthma, exposure to insecticides, presence of cockroaches, smoking, obstructive sleep apnea, and recurrent upper respiratory infections. Targeted interventions are crucial and should focus on lifestyle improvements, allergen identification, cockroach control, smoking cessation, reducing insecticide exposure, and promoting a safe environment. TRIAL REGISTRATION: This review's protocol was pre-registered with the International Prospective Register of Systematic Reviews (PROSPERO registration number CRD42023491222).

Differences between oscillometry measurements obtained by MostGraph-01 and MasterScreen-IOS in patients with asthma.

BACKGROUND: Oscillometry devices (also termed forced oscillation technique) devices such as MasterScreen-IOS® (Jaeger, Hochberg, Germany) and MostGraph-01® (Chest, Tokyo, Japan) are useful for obtaining physiological assessments in patients with obstructive lung diseases, including asthma. However, as oscillometry measurements have not been fully compared between MasterScreen-IOS® and MostGraph-01® in patients with asthma, it is unknown whether there are differences in the measurements between the devices. This study aimed to determine whether there is any difference in oscillometry measurements obtained using the two devices in patients with asthma. METHODS: Oscillometry measurements obtained using MasterScreen-IOS® and MostGraph-01® were retrospectively evaluated in 95 patients with asthma at Juntendo University Hospital between October 2009 and November 2009. RESULTS: There was a strong positive correlation in the measurements between the two devices. However, the values of R5, R20, ALX and Fres were lower when measured with MostGraph-01® than with MasterScreen-IOS®, and vice versa for the values of X5. The results were used in correction equations to convert oscillometry parameters measured using MasterScreen-IOS® to those measured using MostGraph-01®. CONCLUSIONS: To our knowledge, this is the first report to compare MostGraph-01® and MasterScreen-IOS® devices using practical clinical data obtained in patients with asthma. The values obtained by both devices can be interpreted in a similar way, although there is slight variation. The conversion equations produced in this study may assist to compare the oscillometry measurements obtained by each of the two devices.

Salience network resting state functional connectivity during airway inflammation in asthma: A feature of mental health resilience?

BACKGROUND: Inflammation is an established contributor to the pathophysiology of depression and the prevalence of depression in those with chronic inflammatory disease is two- to four-fold higher than the general population. Yet little is known about the neurobiological changes that confer depression or resilience to depression, that occur when episodes of heightened inflammation are frequent or span many years. METHODS: We used an innovative combination of longitudinal resting state functional magnetic resonance imaging coupled to segmental bronchial provocation with allergen (SBP-Ag) to assess changes in resting state functional connectivity (rsFC) of the salience network (SN) caused by an acute inflammatory exacerbation in twenty-six adults (15 female) with asthma and varying levels of depressive symptoms. Eosinophils measured in bronchoalveolar lavage fluid and blood provided an index of allergic inflammation and the Beck Depression Inventory provided an index of depressive symptoms. RESULTS: We found that in those with the highest symptoms of depression at baseline, SN rsFC declined most from pre- to post-SBP-Ag in the context of a robust eosinophilic response to challenge, but in those with low depressive symptoms SN rsFC was maintained or increased, even in those with the most pronounced SBP-Ag response. CONCLUSIONS: Thus, the maintenance of SN rsFC during inflammation may be a biomarker of resilience to depression, perhaps via more effective orchestration of large-scale brain network dynamics by the SN. These findings advance our understanding of the functional role of the SN during inflammation and inform treatment recommendations for those with comorbid inflammatory disease and depression.

Imagining the severe asthma decision trees of the future.

INTRODUCTION: There are no validated decision-making algorithms concerning severe asthma (SA) management. Future risks are crucial factors and can be derived from SA trajectories. AREAS COVERED: The future severe asthma-decision trees should revisit current knowledge and gaps. A focused literature search has been conducted. EXPERT OPINION: Asthma severity is currently defined a priori, thereby precluding a role for early interventions aiming to prevent outcomes such as exacerbations (systemic corticosteroids exposure) and lung function decline. Asthma 'at-risk' might represent the ultimate paradigm but merits longitudinal studies considering modern interventions. Real exacerbations, severe airway hyperresponsiveness, excessive T2-related biomarkers, noxious environments and patient behaviors, harms of OCS and high-doses inhaled corticosteroids (ICS), and low adherence-to-effectiveness ratios of ICS-containing inhalers are predictors of future risks. New tools such as imaging, genetic, and epigenetic signatures should be used. Logical and numerical artificial intelligence may be used to generate a consistent risk score. A pragmatic definition of response to treatments will allow development of a validated and applicable algorithm. Biologics have the best potential to minimize the risks, but cost remains an issue. We propose a simplified six-step algorithm for decision-making that is ultimately aiming to achieve asthma remission.

The Lymphatic Highway: How Lymphatics Drive Lung Health and Disease.

The pulmonary lymphatic system has emerged as a critical regulator of lung homeostasis and a key contributor to the pathogenesis of respiratory diseases. As the primary conduit responsible for maintaining fluid balance and facilitating immune cell trafficking, the integrity of lymphatic vessels is essential for preserving normal pulmonary structure and function. Lymphatic abnormalities manifest across a broad spectrum of pulmonary disorders, underscoring their significance in respiratory health and disease. This review provides an overview of pulmonary lymphatic biology and delves into the involvement of lymphatics in four major lung diseases: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and lung transplant rejection. We examine how lymphatic abnormalities manifest in each of these conditions and investigate the mechanisms through which lymphatic remodeling and dysfunction contribute to disease progression. Furthermore, we explore the therapeutic potential of targeting the lymphatic system to ameliorate these debilitating respiratory conditions. Despite the current knowledge, several crucial questions remain unanswered, such as the spatial and temporal dynamics of lymphatic changes, the molecular crosstalk between lymphatics and the lung microenvironment, and the distinction between protective versus detrimental lymphatic phenotypes. Unraveling these mysteries holds the promise of identifying novel molecular regulators, characterizing lymphatic endothelial phenotypes, and uncovering bioactive mediators. By harnessing this knowledge, we can pave the way for the development of innovative disease-modifying therapies targeting the lymphatic highway in lung disorders.

[Research progress on eosinophil heterogeneity in asthma].

Asthma is a heterogeneous disease characterized by chronic airway inflammation. More than half of asthma cases are induced by allergens. Eosinophils accumulate in large numbers in the airways, and their number is closely related to the severity of asthma. In recent years, extensive research has been conducted on the pathogenesis of eosinophils in asthma and the targeted therapeutic drugs for them. This article mainly reviews the research progress on the important role of eosinophil heterogeneity in the occurrence and development of asthma, and provides ideas for the personalized and precise treatment of asthma in the future.

Association of naples prognostic score and lung health: A population-based study.

BACKGROUND: The Naples Prognostic Score (NPS) is a novel indicator of inflammatory and nutritional status, but its relationship to lung health is unknown. OBJECTIVE: To evaluate the relationship of NPS to lung health problems. METHODS: A total of 15,600 participants aged 20 years or older with an available assessment of chronic lung diseases were enrolled from the National Health and Nutrition Examination Survey 2007-2012. The NPS was calculated based on serum albumin, total cholesterol, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Associations of NPS with chronic lung disease (diagnosed asthma, chronic bronchitis, and emphysema), respiratory symptoms (cough, phlegm production, wheeze, and exertional dyspnea), and spirometric measurements (FEV1, FVC, and obstructive or restrictive spirometry pattern) were evaluated. Kaplan-Meier survival analysis and multiple Cox regressions were used to assess the significance of NPS in relation to all-cause mortality and chronic lower respiratory diseases mortality in participants. Furthermore, to comprehensively assess the association between NSP and chronic lower respiratory diseases mortality, Fine-Gray subdistribution hazards model was performed to analyze non-chronic lower respiratory diseases mortality as a competitive risk. RESULTS: People with a higher NPS score were associated with greater odds of asthma, chronic bronchitis, respiratory symptoms (including phlegm production, wheeze, and exertional dyspnea), and a greater risk of obstructive and restrictive spirometry. A higher NPS score was significantly associated with decreased FEV1 and FVC in both overall participants and those with lung health problems. Longitudinally, we found that those in the category with highest NPS were at greater risk of all-cause mortality and chronic lower respiratory diseases mortality in those with chronic lung disease, and respiratory symptoms. CONCLUSIONS: An elevated NPS is associated with a host of adverse pulmonary outcomes. Prospective studies to define NPS as a biomarker for impaired lung health are warranted.

[The silent correlate of rhinitis on lower airway]. / El impacto silencioso de la rinitis sobre la vía aérea inferior.

The respiratory tract, from the nose to the lung, behaves as an anatomical and pathophysiological unit under a holistic model. Lower airway abnormalities, such as bronchial hyperresponsiveness, reduced lung function and inflammation of the bronchial mucosa without clinical expression, have been observed in patients with rhinitis without asthma. These would be the consequence of a common systemic inflammatory phenomenon with simultaneous impact on the nose and lung. For unknown reasons, these patients do not exhibit a full clinical expression, which could mean an increased risk of developing asthma. In this review we address the frequency and characteristics of existing pulmonary abnormalities in children and adolescents with chronic rhinitis that derive from our previous research and, more recently, within the project "Allergic Respiratory Disease: The United Airway Concept" supported by the Universidad Católica de Córdoba, and a comparative analysis with the evidence provided by other authors in the medical literature.

El aparato respiratorio, desde la nariz al pulmón, se comporta como una unidad anatómica y fisiopatológica bajo un modelo holístico. Se han observado alteraciones pulmonares sin traducción clínica en pacientes con rinitis sin asma, que se manifiestan como hiperreactividad bronquial, reducción de la función pulmonar e inflamación bronquial. Estas serían consecuencia de un fenómeno inflamatorio sistémico con impacto simultáneo en nariz y pulmón, que por razones desconocidas no tiene una expresión clínica completa, pero que podrían significar un mayor riesgo de desarrollo de asma. En esta revisión abordamos la frecuencia y características de las anormalidades pulmonares existentes en niños y adolescentes con rinitis crónica derivadas de nuestras investigaciones previas y, más recientemente, del proyecto "Enfermedad Alérgica Respiratoria: El Concepto de Unidad de la Vía Aérea", línea de investigación acreditada por la Universidad Católica de Córdoba y un análisis comparativo con las evidencias aportadas por otros autores en la literatura médica.

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.