Precision Medicine and Childhood Asthma: A Guide for the Unwary

Many thousands of articles relating to asthma appear in medical and scientific journals each year, yet there is still no consensus as to how the condition should be defined. Some argue that the condition does not exist as an entity and that the term should be discarded. The key feature that distinguishes it from other respiratory diseases is that airway smooth muscles, which normally vary little in length, have lost their stable configuration and shorten excessively in response to a wide range of stimuli. The lungs’ and airways’ limited repertoire of responses results in patients with very different pathologies experiencing very similar symptoms and signs. In the absence of objective verification of airway smooth muscle (ASM) lability, over and underdiagnosis are all too common. Allergic inflammation can exacerbate symptoms but given that worldwide most asthmatics are not atopic, these are two discrete conditions. Comorbidities are common and are often responsible for symptoms attributed to asthma. Common amongst these are a chronic bacterial dysbiosis and dysfunctional breathing. For progress to be made in areas of therapy, diagnosis, monitoring and prevention, it is essential that a diagnosis of asthma is confirmed by objective tests and that all co-morbidities are accurately detailed.

Neural correlate of reduced respiratory chemosensitivity during chronic epilepsy

While central autonomic cardiorespiratory dysfunction underlies sudden unexpected death in epilepsy (SUDEP), the specific neural mechanisms that lead to SUDEP remain to be determined. Here we took an advantage of single cell neuronal Ca2+ imaging and intrahippocampal kainic acid (KA)-induced chronic epilepsy in mice to investigate progressive changes in key cardiorespiratory brainstem circuits during chronic epilepsy. Following induction of status epilepticus (SE), we observed that the adaptive ventilatory responses to hypercapnia were reduced in mice with chronic epilepsy for 5 weeks post-SE. These changes were paralleled by reduced chemosensitivity of neurons in the retrotrapezoid nucleus (RTN), an important centre for respiratory chemosensitivity. Over the same period, chemosensory responses of the presympathetic RVLM neurons showed a slower decrease. Mice with chronic epilepsy were more sensitive to chemoconvulsants and exhibited a greatly reduced latency to seizure induction compared to naive mice. This enhanced sensitivity to seizures, which invade the RTN, puts the chemosensory circuits at further risk and increases the chances of terminal apnoea. Our findings establish a dysfunctional breathing phenotype with its RTN neuronal correlate in mice with chronic epilepsy and suggests a functional non-invasive biomarker test, based on respiratory chemosensitivity, to identify people with epilepsy at risk of SUDEP.

An Overview of the Obese-Asthma Phenotype in Children

Asthma is the most common chronic disease in childhood. Overweight and obesity are included among the comorbidities considered in patients with difficult-to-treat asthma, suggesting a specific phenotype of the disease. Therefore, the constant increase in obesity prevalence in children and adolescents raises concerns about the parallel increase of obesity-associated asthma. The possible correlation between obesity and asthma has been investigated over the last decade by different authors, who suggest a complex multifactorial relationship. Although the particular non-eosinophilic endotype of obesity-related asthma supports the concept that high body weight precedes asthma development, there is ongoing debate about the direct causality of these two entities. A number of mechanisms may be involved in asthma in combination with obesity disease in children, including reduced physical activity, abnormal ventilation, chronic systemic inflammation, hormonal influences, genetics and additional comorbidities, such as gastroesophageal reflux and dysfunctional breathing. The identification of the obesity-related asthma phenotype is crucial to initiate specific therapeutic management. Besides the cornerstones of asthma treatment, lifestyle should be optimized, with interventions aiming to promote physical exercise, healthy diet, and comorbidities. Future studies should clarify the exact association between asthma and obesity and the mechanisms underlying the pathogenesis of these two related conditions with the aim to define personalized therapeutic strategies for asthma management in this population.

The Need for Testing—The Exercise Challenge Test to Disentangle Causes of Childhood Exertional Dyspnea

Exertional dyspnea is a common symptom in childhood which can induce avoidance of physical activity, aggravating the original symptom. Common causes of exertional dyspnea are exercise induced bronchoconstriction (EIB), dysfunctional breathing, physical deconditioning and the sensation of dyspnea when reaching the physiological limit. These causes frequently coexist, trigger one another and have overlapping symptoms, which can impede diagnoses and treatment. In the majority of children with exertional dyspnea, EIB is not the cause of symptoms, and in asthmatic children it is often not the only cause. An exercise challenge test (ECT) is a highly specific tool to diagnose EIB and asthma in children. Sensitivity can be increased by simulating real-life environmental circumstances where symptoms occur, such as environmental factors and exercise modality. An ECT reflects daily life symptoms and impairment, and can in an enjoyable way disentangle common causes of exertional dyspnea.

Identification and management of dysfunctional breathing in primary care

Dysfunctional breathing can lead to a range of symptoms that can be confused with neurological, respiratory and cardiac disease. Heather Henry and Charlotte Wells give an overview of the signs, symptoms, diagnosis and treatment of this condition General practice nurses (GPNs) are often on the front-line of respiratory assessment. Dysfunctional breathing (often termed breathing pattern disorder) is a term that relates to changes in breathing patterns. Since dysfunctional breathing can be confused with neurological, respiratory and cardiac disease, this article will help GPNs to understand the signs, symptoms, diagnosis and treatment.

Development of the 8-Item Phlegm Pattern Questionnaire (PPQ-8) Using Rasch Analysis

The 25-item Phlegm Pattern Questionnaire (PPQ) has been widely used to examine the relationship between the phlegm pattern (PP), quality of life, tongue colour, vocal qualities, and dysfunctional breathing. However, the concerns of response burden and differences in the respondent’s abilities or item difficulty for the original version of the PPQ have not been sufficiently addressed. This study aimed to develop a short-form PPQ using Rasch analysis, an item response theory. Based on the retrospective data, the response order, differential item functioning (DIF), dimensionality, reliability, concurrent validity, and fitting errors were examined for 291 normal participants and 61 inpatients. The discriminative ability of the short-form PPQ was examined using receiver operating characteristic curve analysis. Along with Rasch analysis, another short-form PPQ was developed using equidiscriminative item-total correlation (EITC) analysis and the results between the two short-form PPQs were compared accordingly. Rasch analysis results suggested a 6-point response category for the PPQ, and finally, 8 items without fitting errors or DIF variability were selected for the PPQ (PPQ-8). The PPQ-8 had satisfactory reliability (person separation index = 2.23), unidimensionality (unexplained variance in the first contrast = 1.598), fitting levels (infit mean square, 0.80–1.39; outfit mean square, 0.79–1.34), sensitivity (70.5%), and specificity (76.5%). The PPQ-8 had a moderate discriminative ability of the PP (area under the curve = 0.759), and the cut-off point was 23. Although the 8-item PPQ developed using EITC analysis showed similar levels of reliability, validity, and discriminative ability of the PP to the PPQ-8, it could not present the information of item hierarchy and differences in the respondents’ abilities. In conclusion, the PPQ-8 by Rasch analysis is recommended for future use to evaluate the clinical severity of PP.

Neck Pain and Disability: Are They Related to Dysfunctional Breathing and Stress?

Purpose: People with neck pain are likely to have negative respiratory findings. The purpose of this study was to investigate the relationship between neck pain and dysfunctional breathing and to examine their relationship to stress. Method: This cross-sectional study included 49 participants with neck pain and 49 age- and sex-matched controls. We measured neck pain using the numeric rating scale (NRS); neck disability using the Neck Disability Index (NDI); dysfunctional breathing using the Nijmegen Questionnaire (NQ), Self-Evaluation of Breathing Questionnaire (SEBQ), breath hold time, and respiratory rate (RR); and stress using the Perceived Stress Scale (PSS). Results:Participants with neck pain scored higher on the NQ ( p < 0.001) and the SEBQ ( p < 0.001) than controls. NQ and SEBQ scores correlated moderately with NDI scores ( r > 0.50; 95% CI: 0.25, 0.68 and 0.33, 0.73, respectively) and PSS scores ( r > 0.50; 95% CI: 0.29, 0.78 and 0.31, 0.73, respectively). SEBQ scores showed a fair correlation with NRS scores and RR a fair correlation with NDI scores. Conclusions: Participants with neck pain had more dysfunctional breathing symptoms than participants without neck pain, and dysfunctional breathing was correlated with increased neck disability and increased stress. The NQ and SEBQ can be useful in assessing dysfunctional breathing in patients with neck pain.