B.S. Jayaraj

Serum levels of IL-10, IL-17F and IL-33 in patients with asthma: a case–control study

Abstract Objectives: The development of inflammation in asthma involves an intricate network of cytokines that recruit and activate numerous immune cells. This study was aimed to compare serum levels of IL-10, IL-17F, and IL-33 in asthmatic patients and non-asthmatic controls and correlate cytokine levels to asthma severity and various clinical, spirometric, and laboratory variables. Methods: Using ELISA, serum levels of IL-10, IL-17F, and IL-33 were evaluated in 44 asthmatics (14 mild persistent, 15 moderate persistent, and 15 severe persistent) and 44 controls. Results: This is one of the first reports showing a significant difference in serum levels of asthma-associated cytokines, anti-inflammatory IL-10, and pro-inflammatory IL-17F and IL-33, in the same subset of asthmatic patients. Our results showed diminished level of IL-10 and elevated levels of IL-17F and IL-33 in asthmatics than in controls (p < 0.001). Assessment of cytokine levels between subjects of different gender, age group, and BMI showed non-significant differences. Correlation analysis of cytokine levels to clinical variables showed that IL-17F is associated negatively to FVC % predicted (forced vital capacity) and FEV1% predicted (forced expiratory volume in one second) and positively to number of allergens sensitized and FEV1 reversibility. A strong negative correlation was found between IL-10 and IL-33 levels (p = 0.001). Conclusions: Negative correlation between IL-10 and IL-33 levels may reflect a converse relationship between anti-inflammatory and pro-inflammatory cytokines in an individually balanced pattern. The association between IL-17F level and asthmatic phenotypes such as reduced FVC and FEV1, higher degree of sensitization, and post-bronchodilator reversibility needs further assessments.

Validation of a structured questionnaire for COPD and prevalence of COPD in rural area of Mysore: A pilot study.

Background: The prevalence of chronic obstructive pulmonary disease (COPD) is increasing in India and there is a need to study the prevalence of COPD, particularly in the rural areas, which may be most affected due to their lifestyle. Materials and Methods: First stage: Validation of the questionnaire–105 consecutive patients underwent administration of the structured questionnaire and spirometry was used as a gold standard for the diagnosis of COPD. Second stage: Adults above 40 years (n = 900) in two villages of Mysore district were administered with the validated questionnaire, Knowledge and Attitude questionnaire and Fagerstorm questionnaire, to assess nicotine dependency. Results: The questionnaire was found to have a sensitivity of 62.5% and specificity of 87.6% to diagnose COPD. Of the total 900 adults surveyed (Males: 453, Females: 447), the total prevalence of COPD was 7.1%. Males had a higher prevalence (11.1%) compared to females (4.5%). The prevalence of smoking was very high among men at 71.9% and all the women were nonsmokers. The prevalence of COPD was 14.7% in smokers, 19.3% had mild to moderate nicotine dependency and 12.8% were highly dependent. Of the women exposed to regular biomass fuels, the prevalence of COPD was 3.9%, which increased to 4.8% on addition of regular passive smoking. In smoking, male gender and age were significantly associated with COPD (P < 0.05). Conclusion: The structured questionnaire is a useful tool for the screening of COPD in field studies. Smoking and biomass fuel exposure are important risk factors for COPD.

Serum levels of interleukin-13 and interferon-gamma from adult patients with asthma in Mysore.

Serum protein analysis for noninvasive quantification of airway inflammation in asthma is a promising research tool in the field of lung diseases. Cytokines are believed to have major role in inflammatory process of the airways of the lung. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4 and interleukin (IL)-13, and Th1 cells, which secrete interferon (IFN)-gamma in asthma. To test the hypothesis that serum IL-13 and IL-4 levels may be elevated whereas IFN-gamma would be decreased in this cohort of patients, a property that could make them possible candidate biomarkers in determining asthma occurrence and severity, we measured concentrations of IL-4, IL-13 and IFN-gamma in serum samples of 88 subjects (44 normal, 12 with mild asthma, 16 with moderate asthma, and 16 with severe asthma). Serum Levels of IL-4, IL-13, and IFN-gamma were determined by an enzyme-linked immune-sorbent assay (ELISA). Median serum level of IFN-gamma in asthmatic patients was 8.0 pg/ml, while it was 11.4 pg/ml in healthy controls. However, the difference was not significant. Among the different age groups in whom IFN-gamma was assessed, the highest median value in both cases and controls was observed in the age group of 31-40 years. The median serum level of IL-13 was 40.0 pg/ml in asthmatic patients and 58.25 pg/ml in healthy controls. The difference was not significant. On subgroup analysis, no significant difference of IFN-gamma and IL-13 between asthma of different severities was observed. The study also revealed nonsignificant difference of serum cytokines with the duration of asthma, number of allergens, and severity of sensitization. Normal serum levels of IFN-gamma and IL-13 in asthmatic patients suggest their neutral role in the inflammatory process; however, more studies are required to establish the effect of these cytokines in adulthood asthma in different ethnic populations.

A cavitary lesion in the lung crossing the fissure

Lung India • Vol 28 • Issue 3 • Jul Sep 2011 Laboratory findings The CBC count showed hemoglobin of 12.6 g/dl, leucocytosis with shift to left (14000 cells / micro liter, with 89% neutrophils) and an elevated ESR of 80 mm at 1 h. Blood chemistry analysis showed a BUN of 62 mg/dl, a creatinine level of 1.4 mg/dl, and a random blood sugar of 166 mg/dl. Liver function tests and serum electrolytes were within normal limits and he was seronegative for human immunodeficiency virus. ECG showed multifocal atrial tachycardia. Pulmonary function testing revealed a post bronchodilator FEV1 of 52% with insignificant reversibility. Arterial blood gas measurement revealed a PaO2 of 56 mm Hg and combined respiratory and metabolic acidosis. Chest radiograph revealed a cavitating infiltrate in the right lung crossing the minor fissure and a consolidation in the left lung [Figure 1]. Grams staining study of the sputum for three successive days revealed plenty of pus cells and all three samples were negative for acid fast bacillus by conventional ZN staining. Modified acid fast staining using 1% sulfuric acid as the decolorizer revealed branching acid-fast bacilli irregularly stained consistently in all three samples [Figure 2]. Sputum was CASE SUMMARY

Factors influencing severity of community-acquired pneumonia

Introduction: Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in India. There is a need to understand the risk factors associated with severity of CAP in our population. This study was part of the international global initiative for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia study to evaluate MRSA. Methods: A total of 100 consecutive cases of pneumonia admitted to the Department of Pulmonary Medicine in a tertiary care hospital were recruited in the study during March–July 2015. The severity of pneumonia was assessed based on the CURB-65 score. Individuals with pneumonia and CURB-65 score >2 were compared with subjects with CURB-65 score ≤2. Individuals were also evaluated for the causative organism and its resistance pattern with specific reference to the presence of MRSA. Results: Mean age of patients was 54.03 years, 66% were men. Patients were managed either in the intensive care unit (42%) or wards/high dependency unit (58%), 22% needed noninvasive ventilation and 18% needed mechanical ventilation within 24 h of admission. On multivariate analysis, prior respiratory infection (within last 1 year), obesity (body mass index >30), and alcoholism, old age (>60 years) were independently associated risk factors for severe pneumonia. There were no cases of MRSA. In 34% of cases, organisms could be identified. Most common organisms were Klebsiella (8%), influenza (8%), and Pseudomonas (5%). Conclusion: Prior respiratory infection, obesity, alcoholism, and old age (>60 years) were observed to be important risk factors for severe CAP. Prospective studies should evaluate effect of weight reduction and cessation of alcohol consumption on recurrences of pneumonia in this population and on the severity of pneumonia.

Linoleic acid metabolite leads to steroid resistant asthma features partially through NF-κB

Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15–lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that HODE administration leads to steroid unresponsiveness in an otherwise steroid responsive model of allergic airway inflammation (AAI). HODE treatment to allergic mice further increased airway hyperresponsiveness and goblet metaplasia. Treatment with dexamethasone was associated with increased neutrophilic inflammation in HODE treated allergic mice; unlike control allergic mice that showed resolution of inflammation. HODE induced loss of steroid sensitivity was associated with increased p-NFkB in mice and reduced GR-α transcript levels in cultured human bronchial epithelia. In summary, HODE modifies typical AAI to recapitulate many of the phenotypic features seen in severe steroid unresponsive asthma. We speculate that since HODE is a natural metabolite, it may be relevant to the increased asthma severity and steroid insensitivity in patients who are obese or consume high fat diets. Further characterization of HODE induced steroid insensitivity may clarify the mechanisms.