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2.
Respir Res ; 22(1): 10, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413387

RESUMO

BACKGROUND: Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. METHODS: We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. RESULTS: ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. CONCLUSION: Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.


Assuntos
/biossíntese , Asma/enzimologia , Furina/biossíntese , Neutrófilos/enzimologia , Serina Endopeptidases/biossíntese , Escarro/enzimologia , Adulto , Asma/epidemiologia , Asma/genética , /epidemiologia , Estudos de Coortes , Feminino , Furina/genética , Humanos , Masculino , Pessoa de Meia-Idade , Serina Endopeptidases/genética , Índice de Gravidade de Doença
3.
Clin Exp Allergy ; 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33342006

RESUMO

BACKGROUND: Airway remodelling, which may include goblet cell hyperplasia / hypertrophy, changes in epithelial integrity, accumulation of extracellular matrix components, smooth muscle hypertrophy and thickening of the lamina reticularis, is a feature of severe asthma and contributes to the clinical phenotype. OBJECTIVE: Within the U-BIOPRED severe asthma study, we have assessed histological elements of airway remodelling and their relationship to computed tomography (CT) measures of proximal airway dimensions. METHODS: Bronchial biopsies were collected from two severe asthma groups, one non-smoker (SAn, n = 28) and one current/ex-smoker (SAs/ex, n = 13), and a mild-moderate asthma group (MMA, n = 28) classified and treated according to GINA guidelines, plus a healthy control group (HC, n = 33). Movat's pentachrome technique was used to identify mucin, elastin and total collagen in these biopsies. The number of goblet cells (mucin+) was counted as a percentage of the total number of epithelial cells and the percentage mucin epithelial area measured. The percentage area of elastic fibres and total collagen within the submucosa was also measured, and the morphology of the elastic fibres classified. Participants in the asthma groups also had a CT scan to assess large airway morphometry. RESULTS: The submucosal tissue elastin percentage was higher in both severe asthma groups (16.1% SAn, 18.9% SAs/ex) compared with the HC (9.7%) but did not differ between asthma groups. There was a positive relationship between elastin and airway wall area measured by CT (n = 18-20, rho=0.544, p = 0.024), which also related to an increase in elastic fibres with a thickened lamellar morphological appearance. Mucin epithelial area and total collagen were not different between the four groups. Due to small numbers of suitable CT scans, it was not feasible to compare airway morphometry between the asthma groups. CONCLUSION: These findings identify a link between extent of elastin deposition and airway wall thickening in severe asthma.

5.
Exp Ther Med ; 20(6): 278, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33200003

RESUMO

Bronchial thermoplasty (BT) is a treatment to reduce the airway smooth muscle mass by delivering radiofrequency thermal energy to the airways. BT is used in patients with severe asthma. The present study reported on cases of pneumothorax directly after BT and retrospectively analyzed early radiologic and bronchoscopic modifications after BT. The clinical data and radiologic and bronchoscopic findings of 12 patients with severe asthma who were subjected to BT between July 2014 and October 2017 were analyzed. A total of 33 chest radiographs were collected within 18-24 h after BT. Radiological abnormalities were observed in 32 radiographs as atelectasis (53.1%), peribronchial consolidations (84.4%), pleural effusion (18.8%), effusion in oblique fissures (3.1%), pleural thickening (6.3%) and pneumothorax (3.1%). Of note, one patient suffered pneumothorax after the third BT session and underwent chest drain insertion, followed by mechanical ventilation at the intensive care unit and multiple bronchoscopic interventions, which revealed extensive phlegm plugs. A total of six patients with worsened symptoms and lobar atelectasis also required bronchoscopic intervention, which revealed that phlegm plugs occluded the bronchus in the treated lobe. No bronchoscopic intervention was required in the remaining five patients. During 16-30 days of follow-up, 95.7% of the findings on chest radiography were resolved. To the best of our knowledge, the present study reported the first case of pneumothorax following BT. Early radiologic modifications such as atelectasis and peribronchial consolidations appear common after BT. However, whether bronchoscopic intervention is required for atelectasis following BT warrants further investigation. Of note, BT should be audited and recorded in detail to ideally contribute to a framework of clinical trials to improve risk-benefit evaluations and the selection of patients likely to benefit from treatment.

6.
Sci Total Environ ; : 143553, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33239200

RESUMO

Particulate matter (PM) is a crucial health risk factor for respiratory and cardiovascular diseases. The smaller size fractions, ≤2.5 µm (PM2.5; fine particles) and ≤0.1 µm (PM0.1; ultrafine particles), show the highest bioactivity but acquiring sufficient mass for in vitro and in vivo toxicological studies is challenging. We review the suitability of available instrumentation to collect the PM mass required for these assessments. Five different microenvironments representing the diverse exposure conditions in urban environments are considered in order to establish the typical PM concentrations present. The highest concentrations of PM2.5 and PM0.1 were found near traffic (i.e. roadsides and traffic intersections), followed by indoor environments, parks and behind roadside vegetation. We identify key factors to consider when selecting sampling instrumentation. These include PM concentration on-site (low concentrations increase sampling time), nature of sampling sites (e.g. indoors; noise and space will be an issue), equipment handling and power supply. Physicochemical characterisation requires micro- to milli-gram quantities of PM and it may increase according to the processing methods (e.g. digestion or sonication). Toxicological assessments of PM involve numerous mechanisms (e.g. inflammatory processes and oxidative stress) requiring significant amounts of PM to obtain accurate results. Optimising air sampling techniques are therefore important for the appropriate collection medium/filter which have innate physical properties and the potential to interact with samples. An evaluation of methods and instrumentation used for airborne virus collection concludes that samplers operating cyclone sampling techniques (using centrifugal forces) are effective in collecting airborne viruses. We highlight that predictive modelling can help to identify pollution hotspots in an urban environment for the efficient collection of PM mass. This review provides guidance to prepare and plan efficient sampling campaigns to collect sufficient PM mass for various purposes in a reasonable timeframe.

8.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33043044

RESUMO

Background: Asthma exacerbations are commonly associated with rhinovirus (RV) infection. Interleukin-33 (IL-33) plays an important role during exacerbation by enhancing Type 2 inflammation. Recently we showed that RV infects bronchial smooth muscle cells (BSMCs) triggering production of interferons and IL-33. Here we compared levels of RV-induced IL-33 in BSMCs from healthy and asthmatic subjects, and explored the involvement of pattern-recognition receptors (PRRs) and downstream signalling pathways in IL-33 expression. Method: BSMCs from healthy and severe and non-severe asthmatic patients were infected with RV1B or stimulated with the PRR agonists poly(I:C) (Toll-like receptor 3 (TLR3)), imiquimod (TLR7) and poly(I:C)/LyoVec (retinoic acid-inducible gene 1 (RIG-I)/melanoma differentiation-associated protein 5 (MDA5)). Knockdown of TLR3, RIG-I and MDA5 was performed, and inhibitors targeting TBK1, nuclear factor-κB (NF-κB) and transforming growth factor (TGF)-ß-activated kinase 1 (TAK1) were used. Gene and protein expression were assessed. Results: RV triggered IL-33 gene and protein expression in BSMCs. BSMCs from patients with non-severe asthma showed higher baseline and RV-induced IL-33 gene expression compared to cells from patients with severe asthma and healthy controls. Furthermore, RV-induced IL-33 expression in BSMCs from healthy and asthmatic individuals was attenuated by knockdown of TLR3. Inhibition of TAK1, but not NF-κB or TBK1, limited RV-induced IL-33. The cytokine secretion profile showed higher production of IL-33 in BSMCs from patients with non-severe asthma compared to healthy controls upon RV infection. In addition, BSMCs from patients with non-severe asthma had higher levels of RV-induced IL-8, TNF-α, IL-1ß, IL-17A, IL-5 and IL-13. Conclusion: RV infection caused higher levels of IL-33 and increased pro-inflammatory and Type 2 cytokine release in BSMCs from patients with non-severe asthma. RV-induced IL-33 expression was mainly regulated by TLR3 and downstream via TAK1. These signalling molecules represent potential therapeutic targets for treating asthma exacerbations.

10.
Respir Res ; 21(1): 262, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046036

RESUMO

BACKGROUND: Mitochondrial damage and dysfunction have been reported in airway and quadriceps muscle cells of patients with chronic obstructive pulmonary disease (COPD). We determined the concomitance of mitochondrial dysfunction in these cells in COPD. METHODS: Bronchial biopsies were obtained from never- and ex-smoker volunteers and COPD patients (GOLD Grade 2) and quadriceps muscle biopsies from the same volunteers in addition to COPD patients at GOLD Grade 3/4 for measurement of mitochondrial function. RESULTS: Decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mtROS) and decreased superoxide dismutase 2 (SOD2) levels were observed in mitochondria isolated from bronchial biopsies from Grade 2 patients compared to healthy never- and ex-smokers. There was a significant correlation between ΔΨm and FEV1 (% predicted), transfer factor of the lung for carbon monoxide (TLCOC % predicted), 6-min walk test and maximum oxygen consumption. In addition, ΔΨm was also associated with decreased expression levels of electron transport chain (ETC) complex proteins I and II. In quadriceps muscle of Grade 2 COPD patients, a significant increase in total ROS and mtROS was observed without changes in ΔΨm, SOD2 or ETC complex protein expression. However, quadriceps muscle of GOLD Grade 3/4 COPD patients showed an increased mtROS and decreased SOD2 and ETC complex proteins I, II, III and V expression. CONCLUSIONS: Mitochondrial dysfunction in the airways, but not in quadriceps muscle, is associated with airflow obstruction and exercise capacity in Grade 2 COPD. Oxidative stress-induced mitochondrial dysfunction in the quadriceps may result from similar disease processes occurring in the lungs.

11.
Front Immunol ; 11: 1957, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983127

RESUMO

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke and characterized by chronic inflammation, alveolar destruction (emphysema) and bronchiolar obstruction. Ozone is a gaseous constituent of urban air pollution resulting from photochemical interaction of air pollutants such as nitrogen oxide and organic compounds. While acute exposure to ozone induces airway hyperreactivity and neutrophilic inflammation, chronic ozone exposure in mice causes activation of oxidative pathways resulting in cell death and a chronic bronchial inflammation with emphysema, mimicking cigarette smoke-induced COPD. Therefore, the chronic exposure to ozone has become a model for studying COPD. We review recent data on mechanisms of ozone induced lung disease focusing on pathways causing chronic respiratory epithelial cell injury, cell death, alveolar destruction, and tissue remodeling associated with the development of chronic inflammation and AHR. The initial oxidant insult may result from direct effects on the integrity of membranes and organelles of exposed epithelial cells in the airways causing a stress response with the release of mitochondrial reactive oxygen species (ROS), DNA, and proteases. Mitochondrial ROS and mitochondrial DNA activate NLRP3 inflammasome and the DNA sensors cGAS and STING accelerating cell death pathways including caspases with inflammation enhancing alveolar septa destruction, remodeling, and fibrosis. Inhibitors of mitochondrial ROS, NLRP3 inflammasome, DNA sensor, cell death pathways, and IL-1 represent novel therapeutic targets for chronic airways diseases underlined by oxidative stress.

13.
Sci Transl Med ; 12(557)2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32817367

RESUMO

Increased prevalence of inflammatory airway diseases including asthma and chronic obstructive pulmonary disease (COPD) together with inadequate disease control by current frontline treatments means that there is a need to define therapeutic targets for these conditions. Here, we investigate a member of the G protein-coupled receptor family, FFA4, that responds to free circulating fatty acids including dietary omega-3 fatty acids found in fish oils. We show that FFA4, although usually associated with metabolic responses linked with food intake, is expressed in the lung where it is coupled to Gq/11 signaling. Activation of FFA4 by drug-like agonists produced relaxation of murine airway smooth muscle mediated at least in part by the release of the prostaglandin E2 (PGE2) that subsequently acts on EP2 prostanoid receptors. In normal mice, activation of FFA4 resulted in a decrease in lung resistance. In acute and chronic ozone models of pollution-mediated inflammation and house dust mite and cigarette smoke-induced inflammatory disease, FFA4 agonists acted to reduce airway resistance, a response that was absent in mice lacking expression of FFA4. The expression profile of FFA4 in human lung was similar to that observed in mice, and the response to FFA4/FFA1 agonists similarly mediated human airway smooth muscle relaxation ex vivo. Our study provides evidence that pharmacological targeting of lung FFA4, and possibly combined activation of FFA4 and FFA1, has in vivo efficacy and might have therapeutic value in the treatment of bronchoconstriction associated with inflammatory airway diseases such as asthma and COPD.

14.
Allergy ; 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32740964

RESUMO

BACKGROUND: Macrophages control innate and acquired immunity, but their role in severe asthma remains ill-defined. We investigated gene signatures of macrophage subtypes in the sputum of 104 asthmatics and 16 healthy volunteers from the U-BIOPRED cohort. METHODS: Forty-nine gene signatures (modules) for differentially stimulated macrophages, one to assess lung tissue-resident cells (TR-Mφ) and two for their polarization (classically and alternatively activated macrophages: M1 and M2, respectively) were studied using gene set variation analysis. We calculated enrichment scores (ES) across severity and previously identified asthma transcriptome-associated clusters (TACs). RESULTS: Macrophage numbers were significantly decreased in severe asthma compared to mild-moderate asthma and healthy volunteers. The ES for most modules were also significantly reduced in severe asthma except for 3 associated with inflammatory responses driven by TNF and Toll-like receptors via NF-κB, eicosanoid biosynthesis via the lipoxygenase pathway and IL-2 biosynthesis (all P < .01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll-like and TNF receptor activation and arachidonic acid metabolism (P < .001) and in TAC2 for the inflammasome and interferon signalling pathways (P < .001). Data were validated in the ADEPT cohort. Module analysis provides additional information compared to conventional M1 and M2 classification. TR-Mφ were enriched in TAC3 and associated with mitochondrial function. CONCLUSIONS: Macrophage activation is attenuated in severe granulocytic asthma highlighting defective innate immunity except for specific subsets characterized by distinct inflammatory pathways.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32667261

RESUMO

RATIONALE: New approaches are needed to guide personalized treatment of asthma. OBJECTIVE: To test if urinary eicosanoid metabolites can direct asthma phenotyping. METHODS: Urinary metabolites of prostaglandins (PGs), cysteinyl-leukotrienes (LTs) and isoprostanes were quantified in the Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy controls (HC). Validation was performed internally in 302 SA subjects followed-up after 12-18 months, and externally in 95 adolescents with asthma. MEASUREMENT AND MAIN RESULTS: Metabolite levels in HC were unrelated to age, BMI and sex, except for the PGE2-pathway. Eicosanoid levels were generally greater in MMA relative to HC, with further elevations in SA. However, PGE2-metabolite levels were either the same or lower in male non-smoking asthmatics as in HC. Metabolite levels were unchanged in asthmatics adherent to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas SA treated with omalizumab had lower levels of LTE4 and the PGD2 metabolite 2,3-dinor-11ß-PGF2α. High levels of LTE4 and PGD2-metabolites were associated with lower lung-function, and increased levels of exhaled nitric oxide and eosinophil markers in blood, sputum and urine in U-BIOPRED and in adolescents with asthma. These type-2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study, and found to be as sensitive to detect T2 inflammation as the established biomarkers. CONCLUSIONS: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new non-invasive approach for molecular phenotyping of adult and adolescent asthma. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

16.
J Allergy Clin Immunol ; 146(5): 1045-1055, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32531371

RESUMO

BACKGROUND: Electronic noses (eNoses) are emerging point-of-care tools that may help in the subphenotyping of chronic respiratory diseases such as asthma. OBJECTIVE: We aimed to investigate whether eNoses can classify atopy in pediatric and adult patients with asthma. METHODS: Participants with asthma and/or wheezing from 4 independent cohorts were included; BreathCloud participants (n = 429), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adults (n = 96), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes pediatric participants (n = 100), and Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory Effects 2 participants (n = 30). Atopy was defined as a positive skin prick test result (≥3 mm) and/or a positive specific IgE level (≥0.35 kU/L) for common allergens. Exhaled breath profiles were measured by using either an integrated eNose platform or the SpiroNose. Data were divided into 2 training and 2 validation sets according to the technology used. Supervised data analysis involved the use of 3 different machine learning algorithms to classify patients with atopic versus nonatopic asthma with reporting of areas under the receiver operating characteristic curves as a measure of model performance. In addition, an unsupervised approach was performed by using a bayesian network to reveal data-driven relationships between eNose volatile organic compound profiles and asthma characteristics. RESULTS: Breath profiles of 655 participants (n = 601 adults and school-aged children with asthma and 54 preschool children with wheezing [68.2% of whom were atopic]) were included in this study. Machine learning models utilizing volatile organic compound profiles discriminated between atopic and nonatopic participants with areas under the receiver operating characteristic curves of at least 0.84 and 0.72 in the training and validation sets, respectively. The unsupervised approach revealed that breath profiles classifying atopy are not confounded by other patient characteristics. CONCLUSION: eNoses accurately detect atopy in individuals with asthma and wheezing in cohorts with different age groups and could be used in asthma phenotyping.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32353491

RESUMO

BACKGROUND: Asthma is a heterogeneous disease characterized by distinct phenotypes with associated microbial dysbiosis. OBJECTIVES: Our aim was to identify severe asthma phenotypes based on sputum microbiome profiles and assess their stability after 12 to 18 months. A further aim was to evaluate clusters' robustness after inclusion of an independent cohort of patients with mild-to-moderate asthma. METHODS: In this longitudinal multicenter cohort study, sputum samples were collected for microbiome profiling from a subset of the Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adult patient cohort at baseline and after 12 to 18 months of follow-up. Unsupervised hierarchical clustering was performed by using the Bray-Curtis ß-diversity measure of microbial profiles. For internal validation, partitioning around medoids, consensus cluster distribution, bootstrapping, and topological data analysis were applied. Follow-up samples were studied to evaluate within-patient clustering stability in patients with severe asthma. Cluster robustness was evaluated by using an independent cohort of patients with mild-to-moderate asthma. RESULTS: Data were available for 100 subjects with severe asthma (median age 55 years; 42% males). Two microbiome-driven clusters were identified; they were characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry results, and concurrent asthma medications (all P values < .05). The cluster 2 patients displayed a commensal-deficient bacterial profile that was associated with worse asthma outcomes than those of the cluster 1 patients. Longitudinal clusters revealed high relative stability after 12 to 18 months in those with severe asthma. Further inclusion of an independent cohort of 24 patients with mild-to-moderate asthma was consistent with the clustering assignments. CONCLUSION: Unbiased microbiome-driven clustering revealed 2 distinct robust phenotypes of severe asthma that exhibited relative overtime stability. This suggests that the sputum microbiome may serve as a biomarker for better characterizing asthma phenotypes.

18.
Eur Respir J ; 55(6)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32241830

RESUMO

As global awareness of air pollution rises, so does the imperative to provide evidence-based recommendations for strategies to mitigate its impact. While public policy has a central role in reducing air pollution, exposure can also be reduced by personal choices. Qualified evidence supports limiting physical exertion outdoors on high air pollution days and near air pollution sources, reducing near-roadway exposure while commuting, utilising air quality alert systems to plan activities, and wearing facemasks in prescribed circumstances. Other strategies include avoiding cooking with solid fuels, ventilating and isolating cooking areas, and using portable air cleaners fitted with high-efficiency particulate air filters. We detail recommendations to assist providers and public health officials when advising patients and the public regarding personal-level strategies to mitigate risk imposed by air pollution, while recognising that well-designed prospective studies are urgently needed to better establish and validate interventions that benefit respiratory health in this context.

19.
Expert Opin Pharmacother ; 21(11): 1345-1358, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32301356

RESUMO

INTRODUCTION: Chronic refractory cough (CRC) is more than a persistent cough, but can cause serious impairment to quality of life. Through remarkable advances in our understanding of the neurobiology of cough, there is realization that CRC can be controlled by novel drugs that target cough reflex pathways. AREAS COVERED: The authors present an overview of the clinical trials of antitussives for CRC, and ongoing clinical trials of novel drugs. They discuss the potential strengths and limitations of each medication, as well as knowledge gaps and uncertainties that should be addressed by future trials of putative CRC treatments. EXPERT OPINION: Currently-available antitussive drugs (i.e., opioids and gabapentin) are centrally-acting drugs primarily used for pain and neuropathic conditions; they were not designed for cough and have limitations with respect to efficacy and safety. Due to the success of gefapixant, a first-in-class P2X3 antagonist, early phase trials with different therapeutic targets in the cough reflex pathways have been conducted; these are expected to control cough hypersensitivity, while preserving protective cough reflex. However, the reported effects of antitussive drugs depend on the clinical context, cough outcome measures or cough characteristics. Further biomarkers are needed to accurately predict responders to different antitussive drugs.


Assuntos
Analgésicos Opioides/uso terapêutico , Antitussígenos/uso terapêutico , Tosse/tratamento farmacológico , Gabapentina/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Doença Crônica , Tosse/metabolismo , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
BMC Pulm Med ; 20(1): 90, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293378

RESUMO

BACKGROUND: Cough and airway eosinophilic inflammation has not been highlighted in hypereosinophilic syndrome (HES). CASE PRESENTATION: We report 2 further cases and reviewed the clinical features and treatment of HES present with cough from the literature. Both cases were middle age male, presenting with chronic cough, airway eosinophilic inflammation and hyper eosinophilia who have been previous misdiagnosed as cough-variant asthma and failed anti-asthma treatment. PDGFRA fusion gene was confirmed in one case, but not in the other case. Both had evidence of myeloproliferative features. The tyrosine kinase inhibitor, imatinib, resulted in complete resolution of eosinophilia and cough. By searching PubMed, we found 8 HES cohorts of 411 cases between 1975 and 2013, where the incidence of cough was 23.11%. Sixteen case reports of HES presented with cough as predominant or sole symptom, with nine male patients with positive PDGFRA fusion gene, who responded well to imatinib. Six of seven patients, who tested negative for the PDGFRA, responded to systemic glucocorticoids. CONCLUSIONS: Cough and airway eosinophilic inflammation is common in some HES patients. PDGFRA+ HES patients present with chronic cough respond well to imatinib. Our case reports indicate that PDGFRA negative HES patients may respond to imatinib as well.

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