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American Journal of Respiratory and... Apr 2022Longitudinal modeling of current wheezing identified similar phenotypes, but their characteristics often differ between studies. We propose that a more comprehensive...
Longitudinal modeling of current wheezing identified similar phenotypes, but their characteristics often differ between studies. We propose that a more comprehensive description of wheeze may better describe trajectories than binary information on the presence/absence of wheezing. We derived six multidimensional variables of wheezing spells from birth to adolescence (including duration, temporal sequencing, and the extent of persistence/recurrence). We applied partition-around-medoids clustering on these variables to derive phenotypes in five birth cohorts. We investigated within- and between-phenotype differences compared with binary latent class analysis models and ascertained associations of these phenotypes with asthma and lung function and with polymorphisms in asthma loci 17q12-21 and (cadherin-related family member 3). Analysis among 7,719 participants with complete data identified five spell-based wheeze phenotypes with a high degree of certainty: never (54.1%), early-transient (ETW) (23.7%), late-onset (LOW) (6.9%), persistent (PEW) (8.3%), and a novel phenotype, intermittent wheeze (INT) (6.9%). FEV/FVC was lower in PEW and INT compared with ETW and LOW and declined from age 8 years to adulthood in INT. 17q12-21 and polymorphisms were associated with higher odds of PEW and INT, but not ETW or LOW. Latent class analysis- and spell-based phenotypes appeared similar, but within-phenotype individual trajectories and phenotype allocation differed substantially. The spell-based approach was much more robust in dealing with missing data, and the derived clusters were more stable and internally homogeneous. Modeling of spell variables identified a novel intermittent wheeze phenotype associated with lung function decline to early adulthood. Using multidimensional spell variables may better capture wheeze development and provide a more robust input for phenotype derivation.
Topics: Adult; Asthma; Cadherin Related Proteins; Cadherins; Humans; Infant; Latent Class Analysis; Membrane Proteins; Phenotype; Respiratory Function Tests; Respiratory Sounds; Risk Factors
PubMed: 35050846
DOI: 10.1164/rccm.202108-1821OC -
Archives of Disease in Childhood Dec 2018Children born preterm have an increased risk of asthma in early childhood. We examined whether this persists at 7 and 11 years, and whether wheezing trajectories across...
OBJECTIVE
Children born preterm have an increased risk of asthma in early childhood. We examined whether this persists at 7 and 11 years, and whether wheezing trajectories across childhood are associated with preterm birth.
DESIGN
Data were from the UK Millennium Cohort Study, which recruited children at 9 months, with follow-up at 3, 5, 7 and 11 years.
OUTCOMES
Adjusted ORs (aOR) were estimated for recent wheeze and asthma medication use for children born <32, 32-33, 34-36 and 37-38 weeks' gestation, compared with children born at full term (39-41 weeks) at 7 (n=12 198) and 11 years (n=11 690). aORs were also calculated for having 'early-remittent' (wheezing at ages 3 and/or 5 years but not after), 'late' (wheezing at ages 7 and/or 11 years but not before) or 'persistent/relapsing' (wheezing at ages 3 and/or 5 and 7 and/or 11 years) wheeze.
RESULTS
Birth <32 weeks, and to a lesser extent at 32-33 weeks, were associated with an increased risk of wheeze and asthma medication use at ages 7 and 11, and all three wheezing trajectories. The aOR for 'persistent/relapsing wheeze' at <32 weeks was 4.30 (95% CI 2.33 to 7.91) and was 2.06 (95% CI 1.16 to 2.69) at 32-33 weeks. Birth at 34-36 weeks was not associated with asthma medication use at 7 or 11, nor late wheeze, but was associated with the other wheezing trajectories. Birth at 37-38 weeks was not associated with wheeze nor asthma medication use.
CONCLUSIONS
Birth <37 weeks is a risk factor for wheezing characterised as 'early-remittent' or 'persistent/relapsing' wheeze.
Topics: Asthma; Child; Child, Preschool; Disease Progression; Female; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Logistic Models; Male; Odds Ratio; Recurrence; Respiratory Sounds; Risk Factors; United Kingdom
PubMed: 29860226
DOI: 10.1136/archdischild-2017-314541 -
PloS One 2018Different phenotypes of wheezing have been described to date but not in early life. We aim to describe wheezing phenotypes between the ages of two months and one year,...
OBJECTIVE
Different phenotypes of wheezing have been described to date but not in early life. We aim to describe wheezing phenotypes between the ages of two months and one year, and assess risk factors associated with these wheezing phenotypes in a large birth cohort.
METHODS
We studied 18,041 infants from the ELFE (French Longitudinal Study of Children) birth cohort. Parents reported wheezing and respiratory symptoms at two and 12 months, and answered a complete questionnaire (exposure during pregnancy, parental allergy).
RESULTS
Children with no symptoms (controls) accounted for 77.2%, 2.1% had had wheezing at two months but no wheezing at one year (intermittent), 2.4% had persistent wheezing, while 18.3% had incident wheezing at one year. Comparing persistent wheezing to controls showed that having one sibling (ORa = 2.19) or 2 siblings (ORa = 2.23) compared to none, nocturnal cough (OR = 5.2), respiratory distress (OR = 4.1) and excess bronchial secretions (OR = 3.47) at two months, reflux in the child at 2 months (OR = 1.55), maternal history of asthma (OR = 1.46) and maternal smoking during pregnancy (OR = 1.57) were significantly associated with persistent wheezing. These same factors, along with cutaneous rash in the child at 2 months (OR = 1.13) and paternal history of asthma (OR = 1.32) were significantly associated with increased odds of incident wheezing. Having one sibling (ORa = 1.9) compared to none, nocturnal cough at 2 months (OR = 1.76) and excess bronchial secretions at 2 months (OR = 1.65) were significantly associated with persistent compared to intermittent wheezing.
CONCLUSION
Respiratory symptoms (cough, respiratory distress, and excessive bronchial secretion) were significantly associated with a high risk of persistent wheezing at one year. Smoking exposure during pregnancy was also a risk factor for persistent and incident wheezing.
Topics: Algorithms; Asthma; Bronchi; Cough; Family Health; Female; France; Humans; Hypersensitivity; Infant; Longitudinal Studies; Male; Maternal Exposure; Phenotype; Pregnancy; Respiration Disorders; Respiratory Sounds; Risk Factors; Siblings; Smoking; Surveys and Questionnaires
PubMed: 29702689
DOI: 10.1371/journal.pone.0196711 -
Frontiers in Bioscience (Elite Edition) Jun 2013Wheeze is both a symptom to parents (reported as noisy breathing) and a sign to clinical staff - with very differing perspectives between parents and clinicians on what...
Wheeze is both a symptom to parents (reported as noisy breathing) and a sign to clinical staff - with very differing perspectives between parents and clinicians on what constitutes "wheeze". The purpose of this article is to consider these differences of understanding from the perspective of different stakeholders so that nobody is "lost in translation". Misunderstandings may lead to epidemiologic and treatment faults. Every effort should be made to educate parents and improve their communications with clinicians.
Topics: Adult; Child; Health Education; Humans; Parents; Physicians; Respiratory Sounds
PubMed: 23747920
DOI: 10.2741/e684 -
Sensors (Basel, Switzerland) Feb 2021The appearance of wheezing sounds is widely considered by physicians as a key indicator to detect early pulmonary disorders or even the severity associated with...
The appearance of wheezing sounds is widely considered by physicians as a key indicator to detect early pulmonary disorders or even the severity associated with respiratory diseases, as occurs in the case of asthma and chronic obstructive pulmonary disease. From a physician's point of view, monophonic and polyphonic wheezing classification is still a challenging topic in biomedical signal processing since both types of wheezes are sinusoidal in nature. Unlike most of the classification algorithms in which interference caused by normal respiratory sounds is not addressed in depth, our first contribution proposes a novel Constrained Low-Rank Non-negative Matrix Factorization (CL-RNMF) approach, never applied to classification of wheezing as far as the authors' knowledge, which incorporates several constraints (sparseness and smoothness) and a low-rank configuration to extract the wheezing spectral content, minimizing the acoustic interference from normal respiratory sounds. The second contribution automatically analyzes the harmonic structure of the energy distribution associated with the estimated wheezing spectrogram to classify the type of wheezing. Experimental results report that: (i) the proposed method outperforms the most recent and relevant state-of-the-art wheezing classification method by approximately 8% in accuracy; (ii) unlike state-of-the-art methods based on classifiers, the proposed method uses an unsupervised approach that does not require any training.
Topics: Algorithms; Humans; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Respiratory Sounds; Signal Processing, Computer-Assisted
PubMed: 33670892
DOI: 10.3390/s21051661 -
Clinical and Experimental Immunology Apr 2021Levels of cytokines are used for in-depth characterization of patients with asthma; however, the variability over time might be a critical confounder. To analyze the...
Levels of cytokines are used for in-depth characterization of patients with asthma; however, the variability over time might be a critical confounder. To analyze the course of serum cytokines in children, adolescents and adults with asthma and in healthy controls and to propose statistical methods to control for seasonal effects. Of 532 screened subjects, 514 (91·5%) were included in the All Age Asthma Cohort (ALLIANCE). The cohort included 279 children with either recurrent wheezing bronchitis (more than two episodes) or doctor-diagnosed asthma, 75 healthy controls, 150 adult asthmatics and 31 adult healthy controls. Blood samples were collected and 25 μl serum was used for analysis with the Bio-Plex Pr human cytokine 27-Plex assay. Mean age, body mass index and gender in the three groups of wheezers, asthmatic children and adult asthmatics were comparable to healthy controls. Wheezers (34·5%), asthmatic children (78·7%) and adult asthmatics (62·8%) were significantly more often sensitized compared to controls (4·5, 22 and 22·6%, respectively). Considering the entire cohort, interleukin (IL)-1ra, IL-4, IL-9, IL-17, macrophage inflammatory protein (MIP)-1- and tumor necrosis factor (TNF)- showed seasonal variability, whereas IL-1β, IL-7, IL-8, IL-13, eotaxin, granulocyte colony-stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, MIP-1 and platelet-derived growth factor (PDGF)-BB did not. Significant differences between wheezers/asthmatics and healthy controls were observed for IL-17 and PDGF-BB, which remained stable after adjustment for the seasonality of IL-17. Seasonality has a significant impact on serum cytokine levels in patients with asthma. Because endotyping has achieved clinical importance to guide individualized patient-tailored therapy, it is important to account for seasonal effects.
Topics: Adolescent; Adult; Algorithms; Asthma; Child; Child, Preschool; Cohort Studies; Cytokines; Female; Humans; Male; Models, Theoretical; Respiratory Sounds; Seasons; Time Factors
PubMed: 33202033
DOI: 10.1111/cei.13550 -
Expert Review of Clinical Immunology Jan 2019: In early childhood, wheezing due to lower respiratory tract illness is often associated with infection by commonly known respiratory viruses such as respiratory... (Review)
Review
: In early childhood, wheezing due to lower respiratory tract illness is often associated with infection by commonly known respiratory viruses such as respiratory syncytial virus (RSV) and human rhinovirus (RV). How respiratory viral infections lead to wheeze and/or asthma is an area of active research. : This review provides an updated summary of the published information on the development of post-viral induced atopy and asthma and the mechanisms involved. We focus on the contribution of animal models in identifying pathways that may contribute to atopy and asthma following respiratory virus infection, different polymorphisms that have been associated with asthma development, and current options for disease management and potential future interventions. : Currently there are no prophylactic therapies that prevent infants infected with respiratory viruses from developing asthma or atopy. Neither are there curative therapies for patients with asthma. Therefore, a better understanding of genetic factors and other associated biomarkers in respiratory viral induced pathogenesis is important for developing effective personalized therapies.
Topics: Animals; Asthma; Disease Models, Animal; Humans; Infant; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory System; Rhinovirus
PubMed: 30370798
DOI: 10.1080/1744666X.2019.1541737 -
Thorax Sep 1992
Topics: Auscultation; Humans; Lung; Lung Diseases; Respiratory Sounds
PubMed: 1440457
DOI: 10.1136/thx.47.9.671 -
Nutrients Mar 2017Evidence suggests that reduced intake of fruit and vegetables may play a critical role in the development of asthma and allergies. The present review aimed to summarize... (Meta-Analysis)
Meta-Analysis Review
Evidence suggests that reduced intake of fruit and vegetables may play a critical role in the development of asthma and allergies. The present review aimed to summarize the evidence for the association between fruit and vegetable intake, risk of asthma/wheeze and immune responses. Databases including PubMed, Cochrane, CINAHL and EMBASE were searched up to June 2016. Studies that investigated the effects of fruit and vegetable intake on risk of asthma/wheeze and immune responses were considered eligible ( = 58). Studies used cross-sectional ( = 30), cohort ( = 13), case-control ( = 8) and experimental ( = 7) designs. Most of the studies ( = 30) reported beneficial associations of fruit and vegetable consumption with risk of asthma and/or respiratory function, while eight studies found no significant relationship. Some studies ( = 20) reported mixed results, as they found a negative association between fruit only or vegetable only, and asthma. In addition, the meta-analyses in both adults and children showed inverse associations between fruit intake and risk of prevalent wheeze and asthma severity ( < 0.05). Likewise, vegetable intake was negatively associated with risk of prevalent asthma ( < 0.05). Seven studies examined immune responses in relation to fruit and vegetable intake in asthma, with = 6 showing a protective effect against either systemic or airway inflammation. Fruit and vegetable consumption appears to be protective against asthma.
Topics: Adolescent; Adult; Asthma; Child; Diet; Feeding Behavior; Fruit; Humans; Inflammation; Respiratory Sounds; Vegetables
PubMed: 28353635
DOI: 10.3390/nu9040341 -
European Journal of Pediatrics Jul 2017There is conflicting evidence of the effectiveness of montelukast in preschool wheeze. A recent Cochrane review focused on its use in viral-induced wheeze; however, such... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
There is conflicting evidence of the effectiveness of montelukast in preschool wheeze. A recent Cochrane review focused on its use in viral-induced wheeze; however, such subgroups are unlikely to exist in real life and change with time, recently highlighted in an international consensus report. We have therefore sought to investigate the effectiveness of montelukast in all children with preschool wheeze (viral-induced and multiple-trigger wheeze). The PubMed, Cochrane Library, Ovid Medline and Ovid EMBASE were screened for randomised controlled trials (RCTs), examining the efficacy of montelukast compared with placebo in children with the recurrent preschool wheeze. The primary endpoint examined was frequency of wheezing episodes. Five trials containing 3960 patients with a preschool wheezing disorder were analysed. Meta-analyses of studies of intermittent montelukast showed no benefit in preventing episodes of wheeze (mean difference (MD) 0.07, 95% confidence interval (CI) -0.14 to 0.29; mean for montelukast 2.68 vs placebo 2.54 (p = 0.5)), reducing unscheduled medical attendances (MD -0.13, 95% CI -0.33 to 0.07; mean for montelukast 1.62 vs placebo 1.78 (p = 0.21)) and reducing oral corticosteroids (MD -0.06, 95% CI -0.16 to 0.02; mean for montelukast 0.35 vs placebo 0.36 (p = 0.25)). The pooled results of the continuous regimen showed no significant difference in the number of wheezing episodes between the montelukast and placebo groups (MD -0.40, 95% CI -1.00 to 0.19; mean for montelukast 2.05 vs placebo 2.37 (p = 0.18)).
CONCLUSIONS
This review highlights that the currently available evidence does not support the use of montelukast in preschool children with recurrent wheeze. We recommend further studies to investigate if a 'montelukast responder' phenotype exists, and how these can be easily identified in the clinical setting. What is Known: • Current guidelines recommend montelukast use in preschool children with recurrent wheeze. • A recent Cochrane review has found montelukast to be ineffective at reducing courses of oral corticosteroids for viral-induced wheeze. What is New: • This meta-analysis has examined all children with preschool wheeze and found that montelukast was not effective at preventing wheezing episodes or reducing unscheduled medical attendances. • A specific montelukast responder phenotype may exist, but such patients should be sought in larger multicentre RCTs.
Topics: Acetates; Anti-Asthmatic Agents; Child; Child, Preschool; Cyclopropanes; Humans; Infant; Models, Statistical; Quinolines; Recurrence; Respiratory Sounds; Respiratory Tract Diseases; Sulfides; Treatment Outcome
PubMed: 28567533
DOI: 10.1007/s00431-017-2936-6