Common inflammatory ground links obesity, insulin resistance, and asthma. As recognition of their interplay, one worsening the natural course of the other, is recognised, questions remain about how ...to adequately address them altogether to improve clinical outcomes. The present manuscript sheds light on the problem, describing possible pathophysiological links, clinical views, and therapeutic challenges, raising questions about what remains to be done, and calling for multidisciplinary treatment of these patients to detect diseases early and adequately address them before they become full-blown and deteriorate their health and quality of life.
Asthma is a common chronic disease, with different underlying inflammatory mechanisms. Identification of asthma endotypes, which reflect a variable response to different treatments, is important for ...more precise asthma management. T2 asthma is characterized by airway inflammation driven by T2 cytokines including interleukins IL-4, IL-5, and IL-13. This study aimed to determine whether induced sputum samples can be used for gene expression profiling of T2-high asthma classified by
,
and
expression. Induced sputum samples were obtained from 44 subjects, among them 36 asthmatic patients and eight controls, and mRNA expression levels of
,
, and
were quantified by RT-qPCR. Overall, gene expression levels of
,
, and
were significantly increased in asthmatic patients' samples compared to controls and there was a high positive correlation between expressions of all three genes. T2 gene mean was calculated by combining the expression levels of all three genes (
,
, and
) and according to T2 gene mean expression in controls, we set a T2-high/T2-low cutoff value. Twenty-four (67%) asthmatic patients had T2-high endotype and those patients had significantly higher eosinophil blood and sputum counts. Furthermore, T2-high endotype was characterized as a more severe, difficult-to-treat asthma, and often uncontrolled despite the use of inhaled and/or oral corticosteroids. Therefore, the majority of those patients (15 63% of 24) needed adjunct biological therapy to control their asthma symptoms/exacerbations. In conclusion, we found that interleukins
,
and
transcripts could be effectively detected in sputum from asthmatic patients. Implementation of T2 gene mean can be used as sputum molecular biomarker to categorize patients into T2-high endotype, characterized by eosinophilia and severe, difficult-to-treat asthma, and often with a need for biological treatment.
Here, we present the case of a 28‐year‐old woman who developed severe and progressive thymoma‐associated constrictive bronchiolitis with bronchiectasis, despite undergoing thymectomy. The disease was ...further complicated by radiation‐induced organizing pneumonia (RIOP), which developed after adjuvant radiotherapy (RT) for Masaoka stage II thymoma. The patient was successfully treated with an urgent lung transplantation (LTx) for irreversible respiratory failure.
We present the case of a 28‐year‐old woman with thymoma who developed severe progressive thymoma‐associated constrictive bronchiolitis with bronchiectasis and a radiation‐induced organizing pneumonia following adjuvant radiation therapy. The patient was successfully treated with urgent lung transplantation for irreversible respiratory failure.
Severe asthma is a complex, multidimensional disease. Optimal treatment, adherence and outcomes require shared decision-making, rooted in mutual understanding between patient and clinician. This ...study used a novel, patient-centred approach to examine the most bothersome aspects of severe asthma to patients, as seen from both perspectives in asthma registries.
Across seven countries, 126 patients with severe asthma completed an open-ended survey regarding most the bothersome aspect(s) of their asthma. Patients' responses were linked with their treating clinician who also completed a free-text survey about each patient's most bothersome aspect(s). Responses were coded using content analysis, and patient and clinician responses were compared. Finally, asthma registries that are part of the SHARP (Severe Heterogeneous Asthma Research collaboration, Patient-centred) Clinical Research Collaboration were examined to see the extent to which they reflected the most bothersome aspects reported by patients.
88 codes and 10 themes were identified. Clinicians were more focused on direct physical symptoms and were less focused on "holistic" aspects such as the effort required to self-manage the disease. Clinicians accurately identified a most bothersome symptom for 29% of patients. Agreement was particularly low with younger patients and those using oral corticosteroids infrequently. In asthma registries, patient aspects were predominantly represented in questionnaires.
Results demonstrated different perspectives and priorities between patients and clinicians, with clinicians more focused on physical aspects. These differences must be considered when treating individual patients, and within multidisciplinary treatment teams. The use of questionnaires that include multifaceted aspects of disease may result in improved asthma research.
Many questions concerning responders (R) and nonresponders (NR) in severe eosinophilic asthma (SEA) after blocking the IL-5 (interleukin 5) pathway are still not clear, especially regarding the early ...parameters of response to biologics in personalized treatment strategies. We evaluated 17 SEA patients treated with anti-IL-5 biologics (16 patients mepolizumab, one patient benralizumab) before the introduction of biologics, and at a week 16 follow-up. Clinical, cellular and immunological parameters in peripheral blood were measured in R and NR. Sputum induction with the measurement of cellular and immunological parameters was performed at 16 weeks only. There were 12 R and 5 NR to biologics. After 16 weeks, there was a significant improvement in percentages of FEV1 (
= 0.001), and asthma control test (ACT) (
= 0.001) in the R group, but not in NR. After 16 weeks, the eosinophils in induced sputum were 27.0% in NR and 4.5% in R (
= 0.05), with no difference in IL-5 concentrations (
= 0.743). Peripheral eosinophilia decreased significantly in NR (
= 0.032) and R (
= 0.002). In patients with SEA on anti-IL-5 therapy, there was a marked difference in airway eosinophilic inflammation between R and NR already at 16 weeks, after anti-IL-5 introduction.
Abstract One of the major asthma susceptibility loci is 17q12-17q21.1, but the relationship between this locus and adult asthma is unclear. Association analysis of 13 single nucleotide polymorphisms ...(SNPs) and haplotypes from 17q12-17q21.1 was performed in 418 adult patients with asthma and 288 controls from Slovenia. Single SNP analysis revealed only marginal associations with adult asthma for SNPs located in GSDMA, GSDMB, ORMDL3 and ZPBP2 genes, and rs7219080 was the most highly associated. Analyses of asthma phenotypes found no association with atopy or lung function, but rs2305480 and rs8066582 were associated with childhood asthma and rs9916279 was associated with asthma in smokers. Notably, haplotypes consisting of rs9916279, rs8066582, rs1042658, and rs2302777 harbouring PSMD3 , CSF3 and MED24 genes were highly associated with asthma. The four most common haplotypes, TCCG, TTTA, CCCA and TTCA, were more frequent in patients with asthma, whereas TTCG, TCCA, TCTA and TTTG were more frequent in controls. Only 3% of asthma patients belonged to haplotypes TTCG, TCCA, TCTA and TTTG compared with nearly one-third (31%) of controls. Associations confirmed that the 17q12-17q21.1 locus harbours a genetic determinant for asthma risk in adults and suggest that in addition to the previously known ORMDL3-GSDM locus, CSF3-PSMD3-MED24 also plays a role in asthma pathogenesis.
Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence. Its underdiagnosis and hence under-treatment is a general ...feature across all countries. This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease. A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms. Postbronchodilator forced expiratory volume in 1 second (FEV
)/forced vital capacity <0.7 or less than the lower limit of normal confirms the presence of airflow limitation, the severity of which can be measured by FEV
% predicted: stage 1 defines COPD with mild airflow limitation, which means postbronchodilator FEV
≥80% predicted. In recent years, an elegant series of studies has shown that "exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment". In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation. Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy. This is an essential issue in COPD. In fact, on one hand, airflow limitation, even mild, can unduly limit the patient's physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease. Therefore, we thought that it was worthwhile to analyze further and discuss this stage of "mild COPD". To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with "mild" airflow limitation. The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind "mild" COPD. Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both.
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