Severe Asthma Group Research Articles

Effects of bronchoscopy on lung function in asthmatics

ABSTRACTBackground: To better understand the changes in pulmonary physiology related to asthma severity following bronchoscopy, we performed scheduled pre- and post-procedure spirometry on subjects undergoing bronchoscopy in our research program. Methods: Control subjects and asthma subjects were recruited for bronchoscopy. On the day of bronchoscopy, subjects underwent spirometry pre-bronchoscopy and then up to three sets within 2 hour following the completion of bronchoscopy. A subset of patients had a second bronchoscopy after 2 weeks of treatment with oral prednisolone (40mg daily). Results: A total of 92 subjects had at least one bronchoscopy (12 control subjects, 56 nonsevere asthma (NSA), 24 severe asthma (SA)). The SA and NSA groups had similar decreases in forced expiratory volume in 1 second (FEV1) (−20±13% vs.−19±16%, p = 0.92) and forced vital capacity (FVC) (−20±12% vs.−20±14%, p = 0.80), but no change in FEV1/FVC ratio. The control and NSA group had more rapid recovery of both FEV1 and FVC by 2 hour compared to the SA group (p = 0.01). In the subset of 36 subjects (22 NSA, 14 SA) who underwent a second bronchoscopy following the administration of oral prednisolone for 14 days, steroids resulted in more rapid recovery of lung function (p < 0.04). Conclusion: Following bronchoscopy the lung function of NSA subjects recovered more quickly than SA subjects. Treatment with oral corticosteroids was associated with a quicker recovery of FEV1 which suggests an inflammatory mechanism for these changes in lung compliance.

The cost of asthma control

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Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma.

Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated. We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs). Peripheral blood neutrophils from patients with SA (n=30) and NSA (n=38) were treated with interleukin (IL)-8 (100ng/mL). Autophagy (light chain 3-II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P<0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P<0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r=-0.700, P=0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups. Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.

Uncovering potential key genes associated with the pathogenesis of asthma: A microarray analysis of asthma-relevant tissues

BackgroundThe present study aimed to discover more potential genes associated with the pathogenesis of asthma. MethodsThe microarray data of GSE67940 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in bronchial alveolar lavage cells from patients with mild-moderate asthma (notSA) and severe asthma (SA) compared with normal controls (NC), respectively. Functional and pathway enrichment analysis, protein–protein interaction (PPI) network analysis were performed upon the identified up- and down-regulated DEGs. Besides, the gene association network based on the common up-regulated and down-regulated genes was generated and transcriptional regulatory pairs of overlapping DEGs in the PPI network were identified. ResultsA total of 104 DEGs (30 up- and 74 down-regulated genes) were identified in notSA vs. NC. Additionally, 2796 DEGs were screened out in SA vs. NC group, including 320 up-regulated DEGs, and 135 down-regulated DEGs. Specially, 41 overlapping DEGs were screened out in notSA vs. NC and SA vs. NC, including 16 common up-regulated genes and 25 common down-regulated genes. No pathways were enriched by the DEGs in notSA vs. NC. DEGs in SA vs. NC were associated with cytokine–cytokine receptor interaction. VEGFA was a hub protein in both the PPI networks of DEGs in notSA vs. NC and SA vs. NC. Gene association network showed that signalling pathways and cytokine–cytokine receptor interaction were involved in. The overlapping VEGFA, and IFRD1, and ZNF331 were regulated by more TFs. ConclusionGenes such as VEGFA, and IFRD1, and ZNF331 may be associated with pathogenesis of asthma.

Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study.

The U-BIOPRED study is a multicentre European study aimed at a better understanding of severe asthma. It included three steroid-treated adult asthma groups (severe nonsmokers (SAn group), severe current/ex-smokers (SAs/ex group) and those with mild-moderate disease (MMA group)) and healthy controls (HC group). The aim of this cross-sectional, bronchoscopy substudy was to compare bronchial immunopathology between these groups.In 158 participants, bronchial biopsies and bronchial epithelial brushings were collected for immunopathologic and transcriptomic analysis. Immunohistochemical analysis of glycol methacrylate resin-embedded biopsies showed there were more mast cells in submucosa of the HC group (33.6 mm-2) compared with both severe asthma groups (SAn: 17.4 mm-2, p<0.001; SAs/ex: 22.2 mm-2, p=0.01) and with the MMA group (21.2 mm-2, p=0.01). The number of CD4+ lymphocytes was decreased in the SAs/ex group (4.7 mm-2) compared with the SAn (11.6 mm-2, p=0.002), MMA (10.1 mm-2, p=0.008) and HC (10.6 mm-2, p<0.001) groups. No other differences were observed.Affymetrix microarray analysis identified seven probe sets in the bronchial brushing samples that had a positive relationship with submucosal eosinophils. These mapped to COX-2 (cyclo-oxygenase-2), ADAM-7 (disintegrin and metalloproteinase domain-containing protein 7), SLCO1A2 (solute carrier organic anion transporter family member 1A2), TMEFF2 (transmembrane protein with epidermal growth factor like and two follistatin like domains 2) and TRPM-1 (transient receptor potential cation channel subfamily M member 1); the remaining two are unnamed.We conclude that in nonsmoking and smoking patients on currently recommended therapy, severe asthma exists despite suppressed tissue inflammation within the proximal airway wall.

Evaluation of quality of life according to asthma control and asthma severity in children and adolescents.

ABSTRACTOBJECTIVE: To evaluate quality of life according to the level of asthma control and degree of asthma severity in children and adolescents. METHODS: We selected children and adolescents with asthma (7-17 years of age) from the Pediatric Pulmonology Outpatient Clinic of the State University of Campinas Hospital de Clínicas, located in the city of Campinas, Brazil. Asthma control and asthma severity were assessed by the Asthma Control Test and by the questionnaire based on the Global Initiative for Asthma, respectively. The patients also completed the Paediatric Asthma Quality of Life Questionnaire (PAQLQ), validated for use in Brazil, in order to evaluate their quality of life. RESULTS: The mean age of the patients was 11.22 ± 2.91 years, with a median of 11.20 (7.00-17.60) years. We selected 100 patients, of whom 27, 33, and 40 were classified as having controlled asthma (CA), partially controlled asthma (PCA), and uncontrolled asthma (UA), respectively. As for asthma severity, 34, 19, and 47 were classified as having mild asthma (MiA), moderate asthma (MoA), and severe asthma (SA), respectively. The CA and the PCA groups, when compared with the NCA group, showed higher values for the overall PAQLQ score and all PAQLQ domains (activity limitation, symptoms, and emotional function; p < 0.001 for all). The MiA group showed higher scores for all of the PAQLQ components than did the MoA and SA groups. CONCLUSIONS: Quality of life appears to be directly related to asthma control and asthma severity in children and adolescents, being better when asthma is well controlled and asthma severity is lower.

Chemokine receptors expression on CD3+ blood cells in bronchial asthma

PurposeChemokines and their receptors participate in pathomechanism of bronchial asthma.The aim of the study was to analyze the pattern of chemokine receptor expression on T cells in severe asthmatics and to compare to mild-to-moderate patients and controls. Material/methodsFlow cytometric analysis of CXCR1, CXCR2, CXCR3, CCR3, CCR4, CCR5, CCR7, CCR8 expression on CD3+CD8− and CD3+CD8+ cells was performed in patients with different severity of chronic asthma and in controls. ResultsPercentages of CD3+CD8+ cells expressing CXCR1 were significantly lower in severe asthmatic than in mild-to-moderate asthmatics and in controls. Percentages of CD3+CD8+ cells expressing CCR7 were significantly lower in the severe asthma group than in control group. Percentages of CD3+CD8− cells expressing CXCR1, CXCR2 and CCR8 were significantly lower in the severe asthma group than in mild-to-moderate asthmatics and in controls. The number of cells CD3+CD8− and CD3+CD8+ expressing of CXCR1 was significantly lower in the group of patients using more than 800μg of budesonide daily than in the group of patients using less than 400μg of budesonide. Percentages of CD3+CD8− cells expressing CXCR3, CCR4 and CCR5 were visibly higher (not significantly) in chronic mild-to-moderate asthma than in healthy controls and severe asthmatics. ConclusionsThese results may indicate impairment of some chemokine expression on T cells in severe asthma patients. Moreover participation of both chemokine receptors related to Th1 and Th2 responses in mild-to-moderate asthma and attenuation of these responses in severe asthma has been suggested.

Airway Remodeling in Preschool Children with Severe Recurrent Wheeze.

Airway wall structure in preschoolers with severe recurrent wheeze is poorly described. To describe airway wall structure and inflammation in preschoolers with severe recurrent wheeze. Flexible bronchoscopy was performed in two groups of preschoolers with severe recurrent wheeze: group 1, less than or equal to 36 months (n = 20); group 2, 36-59 months (n = 29). We assessed airway inflammation, reticular basement membrane (RBM) thickness, airway smooth muscle (ASM), mucus gland area, vascularity, and epithelial integrity. Comparisons were then made with biopsies from 21 previously described schoolchildren with severe asthma (group 3, 5-11.2 yr). RBM thickness was lower in group 1 than in group 2 (3.3 vs. 3.9 μm; P = 0.02), was correlated with age (P < 0.01; ρ = 0.62), and was higher in schoolchildren than in preschoolers (6.8 vs. 3.8 μm; P < 0.01). ASM area was lower in preschoolers than in schoolchildren (9.8% vs. 16.5%; P < 0.01). Vascularity was higher in group 1 than in group 2 (P = 0.02) and group 3 (P < 0.05). Mucus gland area was higher in preschoolers than in schoolchildren (16.4% vs. 4.6%; P < 0.01). Inflammatory cell counts in biopsies were not correlated with airway wall structure. ASM area was higher in preschoolers with atopy than without atopy (13.1% vs. 7.7%; P = 0.01). Airway morphometrics and inflammation were similar in viral and multiple-trigger wheezers. In preschoolers with severe recurrent wheeze, markers of remodeling and inflammation are unrelated, and atopy is associated with ASM. In the absence of control subjects, we cannot determine whether differences observed in RBM thickness and vascularity result from disease or normal age-related development.

Airway inflammatory phenotypes of asthmatic patients

To analyze the airway inflammatory phenotypes and clinical features of severe asthma compared to mild-moderate ("common") asthma. A total of 946 cases of asthma were retrospectively analyzed in our hospital from January 2013 to December 2014. Sixty-one patients were classified to the severe asthma group, and 885 patients to the common asthma group. Severe asthma was diagnosed based on the protocol from ATS/ERS guidelines. All patients received induced sputum cell counts and pulmonary function tests, and 543 of them received fractional exhaled nitric oxide (FeNO) tests. The airway inflammatory phenotypes were defined and the clinical features of patients of severe asthma were studied. The distribution of airway inflammatory phenotypes of asthma was as follows: eosinophilic subtype (46.6%, 441/946), mixed granulocytic subtype (27.5%, 260/946), neutrophilic subtype (21.5%, 203/946), and paucigranulocytic subtype (4.4%, 42/946). There were no differences between the severe asthma group and the common asthma group in the distributions. Compared with common asthma patients, severe asthma patients had higher sputum eosinophil percentages (29.1 % ± 28.5% vs 22.2% ± 25.2%, t = 1.98, P < 0.05), higher FeNO values [(66.4 ± 64.1) ppb vs (48.0 ± 43.7) ppb, P < 0.01], lower percentages of FEV1% pred [(63.7 ± 24.1) % vs (84.7 ± 23.7)%, P < 0.01], and lower ratios of FEV1/FVC [(56.4 ± 15.1) % vs (69.1 ± 14.5)% P < 0.01]. In severe asthma patients, FeNO values were higher in the eosinophilic subtype and mixed granulocytic subtype (P < 0.05). Neutrophilic subtype patients had the lowest sputum eosinophil percentage [(1.8 ± 0.8)%, P < 0.01], the lowest percentage of FEV1% pred [(46.6 ± 16.1)%, P < 0.01], and the lowest ratios of FEV1/FVC [(45.2 ± 16.1)%, P < 0.01]. The common airway inflammatory phenotypes included eosinophilic subtype, mixed granulocytic subtype and neutrophilic subtype, in both severe and common asthma patients. Severe asthma patients had more severe eosinophilic airway inflammation and poorer lung function. Neutrophilic subtype might be the most intractable subtype with severely damaged pulmonary function in severe asthma.

Sleep Duration, Sleep Hygiene, and Insomnia in Adolescents with Asthma

There is a need to understand more about modifiable health behaviors that may be related to asthma control. Sleep is one such health behavior that has received little attention in pediatric asthma research. To examine sleep duration, sleep hygiene, and insomnia in adolescents with and without asthma. Adolescents (n = 298; 51% boys; age range, 12-17 years; 48% with asthma) from the general community completed an online survey that included the International Study of Asthma and Allergies in Childhood questionnaire, the Children's Report of Sleep Patterns, and the Insomnia Severity Index. Sleep duration did not differ between the asthma severity groups, yet more adolescents with severe asthma reported insufficient weekday sleep (44%) versus adolescents without asthma (31%). Significant asthma group differences were found for sleep hygiene, with adolescents with severe asthma reporting poorer sleep hygiene. Almost twice as many adolescents with severe asthma reported clinically significant insomnia than adolescents with mild or no asthma. Sleep hygiene variables were correlated with insomnia, although these associations did not differ between adolescents with and without severe asthma. Finally, both insomnia severity and asthma severity were significant predictors of daytime sleepiness; however, asthma severity accounted for only 2% of the variance compared with 28% of the variance accounted for by insomnia severity. Many adolescents with severe asthma regularly obtain insufficient sleep, have poor sleep hygiene, and experience clinically significant insomnia. It is important to ask adolescents with asthma about sleep duration, sleep hygiene, and insomnia because there are effective interventions that can improve sleep for these youths.

Interleukin-18 −607C/A Gene Polymorphism in Egyptian Asthmatic Children

Asthma is a multifactorial respiratory disease determined by interactions of multiple disease susceptibility genes and environmental factors. Interleukin (IL)-18 is an important cytokine for initiating and perpetuating the catabolic and inflammatory response in allergic asthma. A number of single nucleotide polymorphisms that influence IL-18 production are found in the gene promoter region. The aim of this study was to investigate the association of IL-18 -607C/A promoter polymorphism with asthma and whether this polymorphism influenced the severity of asthma in affected children. The influence of this promoter gene polymorphism on total serum IgE level in studied subjects was also investigated. This study was carried out at the Allergy Clinic of Abu El Reesh Children's Hospital at Cairo University, Egypt. This study included 40 asthmatic children, subdivided into four groups according to different degrees of asthma severity, and 20 apparently healthy subjects as the control group. All cases were subjected to history taking, clinical examination, and the following laboratory investigations: complete blood count, total serum IgE level assay by ELISA and genomic DNA extraction, and analysis for IL-18 -607C/A promoter gene polymorphism using the PCR-RFLP (restriction fragment length polymorphism) technique. In the present study the IL-18 -607AA genotype frequency was higher in cases (22.5 %) than in the control group (15 %); however, the difference was not statistically significant (p = 0.773). No statistically significant difference between the degree of asthma severity and IL-18 -607C/A polymorphism was found (p = 0.489). No significant association could be detected upon comparing the frequencies of C and A alleles among the two studied groups (p = 0.366). Also, no significant differences were demonstrated for the allele frequencies when the intermittent with mild [odds ratio (OR) = 2.72, 95 % CI 1.03-2.33, p = 0.067], intermittent with moderate, and severe (OR = 2.8, 95 % CI 1.01-8.5, p = 0.066) asthma groups were compared. The median value of the total serum IgE level in asthmatic cases with the mutant genotype (AA) was significantly higher [360 IU/L (96.6-1,340 IU/L)] than in the control group [119 IU/L (70.6-158.9 IU/L)] (p = 0.033). No significant statistical difference was encountered regarding the distribution of IL-18 -607C/A genotypes and allele frequencies in asthma patients and healthy controls. Also, there were no significant associations between asthma severity and different genotypes or alleles. The median value of the total serum IgE level in asthmatic cases with the mutant genotype (AA) was significantly higher than in the control group. Thus, IL-18 -607AA genotype frequency might be related to higher total serum IgE.

Clinical significance of small airway obstruction markers in patients with asthma

The role of small airway obstruction in the clinical expression of asthma is incompletely understood. We tested the hypotheses that markers of small airway obstruction are associated with (i) increased asthma severity, (ii) impaired asthma control and quality of life and (iii) frequent exacerbations. Seventy-four adults with asthma and 18 healthy control subjects underwent impulse oscillometry (IOS), multiple breath inert gas washout (MBW), body plethysmography, single-breath determination of carbon monoxide uptake and spirometry. Patients completed the six-point Asthma Control Questionnaire (ACQ-6) and standardized Asthma Quality of Life Questionnaire [AQLQ(S)]. Asthma severity was classified according to the Global Initiative for Asthma (GINA) treatment steps. The putative small airway obstruction markers Sacin , resistance at 5 Hz minus resistance at 20 Hz (R5-R20) and reactance area (AX) were not independently associated with asthma severity, control, quality of life or exacerbations. In contrast, markers of total (R5) and mean airway resistance of large and small airways (R20) were significantly higher in the severe asthma group compared with the mild-moderate group (0.47 vs. 0.37, P < 0.05 for R5; 0.39 vs. 0.31, P < 0.01 for R20). The strongest independent contributors to ACQ-6 score were R20 and forced expiratory volume in one second (% pred.), and the strongest independent contributors to AQLQ(S) score were R20 and forced vital capacity (% pred.). A history of one or more exacerbations within the previous year was independently associated with R20. Previously reported markers of small airway obstruction do not appear to be independently associated with asthma disease expression. In contrast, the IOS parameter R20, a marker of mean airway resistance of both large and small airways, appears to have independent clinical significance. These observations require confirmation in prospective longitudinal studies.

The Portuguese DISABKIDS Asthma Module: a global index of asthma-specific quality of life for children and adolescents

Background: The KIDSCREEN and DISABKIDS questionnaires constitute a modular system for assessing the health-related quality of life (HrQoL) of children/adolescents. Objective: This study was aimed at examining the factorial structure of the Portuguese patient- and parent-reported versions of the DISABKIDS-Asthma Module (AsM) and its invariance across age groups and informants, as well as to examine their reliability and construct validity. Methods: The sample included 140 children/adolescents aged 8–18 years, who were diagnosed with asthma, and one of their parents. Both family members assessed HrQoL at the generic (KIDSCREEN-10), chronic-generic (DISABKIDS-12) and asthma-specific (DISABKIDS-AsM) levels. Asthma severity was classified by physicians using Global Initiative for Asthma (GINA) guidelines. Results: Confirmatory factor analysis attested the factorial validity of the correlated two-factor model of the DISABKIDS-AsM, but the low average variance extracted by each factor (Impact and Worry) suggested that a one-factor structure would better fit the Portuguese data. The one-factor model had an acceptable fit (χ2/df = 1.97; comparative fit index = 0.94; root mean square error of approximation = 0.08) and was invariant between age groups (children vs. adolescents) and informants (patient-reports vs. parent-reports). The resulting global index of asthma-specific HrQoL presented good reliability and convergent validity with the generic and chronic-generic measures. The DISABKIDS instruments also detected significant differences in HrQoL regarding asthma severity groups. Conclusions: The DISABKIDS-AsM may be regarded as a specific one-dimensional questionnaire, which, besides suiting pediatric patients in different developmental stages and enabling reliable proxy-reports, is sensitive to asthma clinical characteristics and is cross-culturally comparable, thus representing a valuable tool for assessing asthma-specific HrQoL as a primary health outcome in clinical practice and research contexts.

The effect of CD14 and TLR4 gene polimorphisms on asthma phenotypes in adult Turkish asthma patients: a genetic study

BackgroundEndotoxins stimulate T helper 1 cell maturation and send a negative signal to T helper 2 polarisation. This causes a decrease IgE levels and prevents atopy (Hygiene hypothesis). It is shown that this response is under genetic control by polymorphisms in CD14 and TLR4 genes in some researchs. We aimed to investigate the effects of genetic variants of CD14 (−) and TLR4 (Asp299Gly, Thr399Ile) genes on asthma phenotypes in adults with asthma.MethodsAsthma patients (n = 131) and healthy control cases (n = 75) were included in the study. Relations between CD14 C-159 T, TLR4 299 and TLR4 399 genotypes and duration of asthma history of allergic rhinitis-dermatitis, total IgE, eosinophil, skin prick test, forced expiratory volume 1 (FEV1) and severity of disease were evaluated. Real time PCR (RT-PCR) was used for genotyping.ResultsFor CD14-159, presence of the C allele (CC + CT) was more frequent among those with low median log (logarithm) IgE levels, but no statistically significant difference in all asthma group (p = 0.09). C allele was significantly correlated with low total IgE levels and T allele with high total IgE levels in atopics (p = 0.04). CC + CT genotype was more frequent in moderate and severe asthma group in atopics (p = 0.049). TLR4 299 and TLR4 399 genotypes and asthma phenotypes were not found to be significantly correlated (p > 0.05).ConclusionsTotal IgE levels were found to be low among patients with the CC + CT genotype, and high among patients with the TT genotype contrary to the results of many other studies, which is therefore an important finding. Another important finding was that the C allele is a risk factor for moderate and severe asthma.

Outcomes of childhood asthma to the age of 50 years

In 1964, The Melbourne Asthma Study was established to describe the spectrum and natural history of childhood asthma. To describe the clinical and lung function outcome of childhood asthma to the age of 50 years. Subjects were invited to complete an interviewer-administered questionnaire, skin prick testing, and measurement of lung function from the age of 7 years to the age of 50 years at 7-year intervals. Of 458 survivors (from the original 484 subjects at recruitment), 346 subjects (76%) participated, of whom, 197 completed lung function measurement. Asthma remission at the age of 50 years was 64% in those with wheezy bronchitis, 47% for those with persistent asthma, and 15% for those with severe asthma in childhood. Multivariable analysis identified severe asthma in childhood (odds ratio [OR] 11.9 [95% CI, 3.4-41.8]), female sex (OR 2.0 [95% CI, 1.1-3.6]), and childhood hay fever (OR 2.0 [95% CI, 1.0-4.0]) as risk factors for "current asthma" at age 50 years. There was no evidence of a difference in the rate of decline in FEV1 (mL/y, 95% CI) between the severe asthma group (15 mL/y [95% CI, 9-22 mL/y]) and all the other recruitment groups: control (16 mL/y [95% CI, 12-20 mL/y]), mild wheezy bronchitis (14 mL/y [95% CI, 8-19 mL/y]), wheezy bronchitis (16 mL/y [95% CI, 11-20 mL/y]), and persistent asthma (19 mL/y [95% CI, 13-24 mL/y]). The clinical and lung function outcome in adult life is strongly determined by asthma severity in childhood. The reduced lung function seen in adults is established in childhood and does not appear to decline more rapidly in adult years despite continuing symptoms.

Defining Severe Asthma In Childhood: A Descriptive Multicenter Study In Turkey

Severe asthma causes significant burden in terms of morbidity and healthcare resource use. Moreover, it is a heterogeneous disease creating difficulty in discrimination/classification. In order to define characteristics of children having high level of asthma treatment and burden, 23 asthma centers of the country recorded patients during one year period. 372 children with asthma were allocated and from those who fit either Severe Asthma Research Program (SARP) or Problematic Severe Asthma (PSA) criteria were defined as severe asthma and the remainder served as controls. According to the criteria of PSA and SARP, 135 and 77 were classified as severe asthma, respectively and majority of the latter group appeared to be a subgroup of PSA. Compared to control group (n:232, moderate asthma), patients in severe asthma group had higher school absenteeism, unscheduled healthcare resource use, admission to an emergency unit, hospitalizations and systemic corticosteroid use within last year and had lower scores for ACT/C-ACT and FEV1 (p<0.05). Patients classified as both PSA&SARP were younger than the patients classified only as PSA and had higher unscheduled healthcare resource use, admission to an emergency unit and lower ACT scores (p<0.05 for each). Children with severe asthma have significantly higher burden compared those with moderate asthma. The use of criteria of PSA for severe asthma causes inclusion of more patients compared the definition of SARP indicating the employment of a wider spectrum for the definition. The utility and value of definitions for severe asthma need to be further determined prospectively

Severe Asthma Phenotyping: The Applicability of Current Proposols in Daily Practice

Background: Severe asthma (SA) is also need to be phenotyping. We aimed to demonstrate the applicability of current definition and classification proposals in daily practice. Methods: SA patients, according to WHO definition of treatment resistant SA, were enrolled from the allergy clinic. The SARP algorith define and WHO proposal were applied to the subjects independently by asthma experts. Demographic and clinical characteristics of the subjects were used for the comparison. Results: Ninety-five (F/M: 68/27) patients with a mean age of 45.97± 9.44 years (range25-71) were enrolled. The patients were grouped as controlled treatmentresistant SA (56%) and uncontrolled treatment resistant SA group (44%). There was no statistically significant difference between the groups but aspirin hypersensitivity. 49% of patients was classified as exacerbators, 26% as fixed airway obstruction group and 23% as undefined (other 2%). Age and mold sensitivity was higher; FEV1/FVC and FEF25-75 were lower in exacerbation-prone SA. More than half of the patients were define clustered at 4 and 5 according to SARP proposol. Patients with fixed obstruction were only in the clusters 4 and 5. Conclusion: Current phenotyping proposols failed to cover all SA patients. Thus, there is still need further investigations in order to explore validity and applicability of the phenotyping of SA.

Changes in interleukin-17 and transforming growth factor beta 1 levels in serum and bronchoalveolar lavage fluid and their clinical significance among children with asthma.

To investigate the changes in the levels of interleukin-17 (IL-17) and transforming growth factor beta 1 (TGF-β1) in serum and bronchoalveolar lavage fluid (BALF) and their clinical significance among children with asthma. A total of 56 children with asthma were divided into moderate or severe asthma (n=37) and mild asthma groups (n=19) and 18 children without asthma were selected as the control group. Cells in BALF were counted under a microscope. The levels of IL-17 and TGF-β1 in serum and BALF were measured using enzyme-linked immunosorbent assay (ELISA). There were no significant differences in total cell count and percentage of macrophages between the two asthma groups and the control group (P>0.05). The percentages of neutrophils, eosinophils and epithelial cells in BALF were significantly higher in the two asthma groups than in the control group (P<0.05). The two asthma groups had significantly higher levels of IL-17 and TGF-β1 in serum and BALF than the control group (P<0.05), and the moderate or severe asthma group had significantly higher levels of IL-17 and TGF-β1 in serum and BALF than in the mild asthma group (P<0.05). The serum levels of IL-17 and TGF-β1 were positively correlated with those in BALF (r=0.935 and 0.943, both P<0.05). In children with asthma, serum IL-17 level was positively correlated with the percentages of neutrophils, eosinophils, and epithelial cells in BALF (r=0.802, 0.799, and 0.674, all P<0.05), and a positive correlation was also seen between serum levels of IL-17 and TGF-β1 (r=0.878, P<0.05). Levels of IL-17 and TGF-β1 in serum and BALF are elevated in children with asthma. IL-17 and TGF-β1 may be involved in the occurrence and development of asthma, and they play important roles in asthma attack and aggravation.

The characteristics of serum circulating immune complexes of patients with atopic asthma with different severity degree

Aim. To evaluate the serum level of pathogenic circulating immune complexes in patients with mild and severe atopic bronchial asthma. Methods. Serum samples of patients with atopic asthma of mild persistent (30 patients) and severe persistent (20 patients) forms were analyzed. The control group consisted of 15 healthy volunteers. To detect the giant, large, medium and small-sized serum immune complexes, 3, 3.5, 4 and 7% polyethyleneglycol-6000 solutions were used. For quantitative evaluation of the immune complexes we measured the ultraviolet optical density at 280 nm wave length. To separate the immune complexes from immunoglobulin, Protein-G-Sepharose was used. Determination of the protein composition of circulating immune complexes was performed by electrophoresis in 8% polyacrylamide gel. Results. The concentration of immune complexes was increased in patients with bronchial asthma compared to healthy donors. Small and medium-sized immune complexes were prevailing, their concentrations correlated with the severity of asthma. Large, medium and small-sized immune complexes participated in immunopathological reactions in patients with both mild and severe asthma, with immune complexes pathogenicity coefficient significantly increased depending on the severity of the disease. Electrophoretic analysis of circulating immune complexes has shown the presence of proteins with molecular weight of 60 kDa in the complexes of all sizes. In the severe asthma group, an antigen fraction with a molecular mass of 36 kDa within the small-sized molecular complexes was revealed. Conclusion. The observed increase of small and medium-sized circulating immune complexes serum levels in patients with bronchial asthma may be an indicator of of these patients predisposal to autoimmune reactions development.

Lipid-laden bronchoalveolar macrophages in asthma and chronic cough

The presence of lipids in alveolar macrophages (AMs) may impair their phagocytic response, and determine airway inflammation and obstruction. To determine the factors such as severity of asthma, chronic cough, airway inflammation and obesity that may influence the presence of lipids in lung macrophages. Bronchoalveolar lavage fluid (BALF) was obtained from 38 asthmatics (21 severe and 17 mild/moderate), 16 subjects with chronic cough and 11 healthy control subjects. The presence of lipids in macrophages was detected using an Oil-red-O stain and an index of lipid-laden macrophages (LLMI) was obtained. LLMI scores were higher in healthy subjects (median 48 [IQR 10-61]) and the severe asthma group (37 [11.5-61]) compared to mild/moderate asthmatics (7 [0.5-37]; p<0.05 each). Subjects reporting a history of gastro-oesophageal reflux disease (GORD) had higher LLMI values (41.5 [11.3-138] versus 13 [0-39.3], p=0.02). There was no significant correlation between LLMI and chronic cough, BAL cell differential counts, FEV1, FEV1/FVC or body mass index (BMI). The reduced LLMI in mild/moderate asthma may be related to lower incidence of GORD. However, this was not related to the degree of airflow obstruction, obesity or airway inflammation.