Understanding the Association Between Obesity and Obstructive Sleep Apnea Syndrome: A Case-Control Study.

Introduction Obstructive sleep apnea (OSA) represents a sleep-related impairment linked to upper airway function. The question of whether OSA drives obesity or if shared underlying factors contribute to both conditions remains unresolved. Hence, this present study aims to understand the interplay between obstructive sleep apnea syndrome (OSAS) and obesity through in-depth analysis of anthropometric data within control subjects and OSA patients. Methodology A case-control study was conducted, which included 40 cases and 40 matched healthy controls. Study participants with reported symptoms of snoring, daytime drowsiness, or both were included in the study. All the study participants underwent comprehensive anthropometric assessments such as height, weight, body mass index (BMI), neck circumference, waist circumference, hip circumference, waist-to-hip ratio, skin-fold thickness, and thickness measurements of biceps, triceps, suprailiac, and subscapular muscles. Results Within the OSA group, significant disparities emerged in mean age, waist circumference, waist-to-hip ratio, and diverse fat accumulations encompassing visceral, subcutaneous, trunk, and subcutaneous leg fat. Notably, skin-fold thickness at specific sites - biceps, triceps, subscapula, and suprailiac - demonstrated considerable augmentation relative to the control group. Furthermore, mean values associated with height, weight, BMI, neck circumference, fat percentage, subcutaneous arm fat, entire arm composition, and trunk skeletal muscle either equaled or exceeded those in the control group. However, statistical significance was not attained in these comparisons. Conclusion This investigation underscored a pronounced correlation between numerous endpoints characterizing OSA patients and markers of obesity. Consequently, addressing altered levels of obesity-linked anthropometric variables through pharmacological interventions might hold promise as a pivotal strategy for improving symptoms associated with OSA.

Assessment of Leptin Levels and Their Correlation With the Severity of Obstructive Sleep Apnea Syndrome: A Case-Control Study.

Background Obstructive sleep apnea (OSA) is characterized by a combination of structural issues in the upper airway and imbalances in the respiratory control system. While numerous studies have linked OSA with obesity, it remains uncertain whether leptin, a hormone associated with fat, plays a role in the functional and anatomical defects that lead to OSA. Therefore, the aim of this study was to investigate whether leptin levels could be used as a predictor of OSA syndrome (OSAS). Methodology A case-control observational study was conducted, enrolling study participants who reported obesity (BMI > 30) within the range of >30 to <35 kg/m2, along with a short neck and a history of snoring, excessive daytime drowsiness, fatigue, or insomnia. Leptin levels and fasting blood sugar (FBS) were measured in all individuals. Additionally, the study evaluated the severity of OSAS using indicators such as the STOP BANG scores, apnea-hypopnea index, uvula grade score, and Epworth Sleepiness Scale scores. Results A total of 80 participants (40 cases and 40 controls) were included in the study. The mean leptin and FBS levels were significantly higher in cases compared to controls. Moreover, leptin levels exhibited a significant correlation with the severity indices of OSAS. Conclusion The study findings indicate that individuals with higher leptin levels tend to exhibit more severe OSAS symptoms. Furthermore, these elevated leptin levels contribute to the worsening of various OSA symptoms. Larger controlled studies have suggested that pharmacologically restoring the altered leptin levels may serve as a beneficial adjunct to treatment for alleviating OSAS symptoms.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

Identification of B cell epitopes of Per a 5 allergen using bioinformatic approach.

BACKGROUND: Immune epitopes of allergens are pivotal for development of novel diagnostic and therapeutic modalities. Present study aims to identify antigenic determinants of Per a 5, a clinically relevant cross reactive cockroach allergen. METHODS: The three dimensional structure of Per a 5 was modelled using Modeller 9v11 software. A combination of sequence and structure based computational tools were employed for predicting B cell epitopes. Epitopes were synthesized and immunoreactivity was assessed by ELISA using cockroach hypersensitive patient's sera. Cross-reactivity potential of predicted epitopes was assessed with SDAP and ConSurf and validated by IgE ELISA with fungal and mite hypersensitive patient's sera. RESULTS: Per a 5 structure exhibited good quality factor in ERRAT and high stereochemical stability. In silico analysis revealed six B cell epitopes (BC-P1 to P6). BC-P3 demonstrated significant IgE binding followed by BC-P2 and BC-P1 with cockroach hypersensitive patient's sera. Per a 5 epitopes demonstrate considerable similarity with broad spectrum of allergens from fungal, mites, helminths, fruits and nuts. Analysis of PD values indicate BC-P4 to be well conserved among dust mite and helminth GSTs (8.89, 10.63 and 10.69 with D. pteronyssinus, W. bancrofti and F. hepatica respectively). ConSurf analysis of Per a 5 revealed specific enrichment of evolutionarily similar amino acid residues in BC-P2 (with fungal and mite GSTs) and BC-P4 (with mite and helminth GSTs). Further, IgE binding analysis of epitopes demonstrate BC-P2, BC-P3 and BC-P5 as high IgE binders in fungal hypersensitive sera while BC-P1, BC-P2, BC-P4 and BC-P5 demonstrated significant IgE binding with mite hypersensitive sera. CONCLUSIONS: Among the predicted epitopes, BC-P3 demonstrates maximal IgE binding ability. Computational analysis suggests strong evolutionary conservation and cross reactive potential of BC-P4 with allergens in dust mite and helminths. ELISA highlights predictive potential of analysing evolutionarily conserved residues for uncovering potentially cross reactive antigenic determinants. GENERAL SIGNIFICANCE: Immune epitopes of Per a 5 were identified for aiding molecular diagnosis and potential cross reactivity.

Identification of a vicilin-like major allergen from Prosopis juliflora exhibiting cross- reactivity with legume food allergens.

BACKGROUND: Prosopis juliflora is a clinically relevant allergic sensitizer worldwide and shares cross-reactivity with allergens from several tree pollen and food. The present study aims to purify and immunobiochemically characterize a major allergen from Prosopis pollen. The allergen was further investigated for its cross-reactivity with legume allergens. METHODS: Prosopis extract was fractionated by Q Sepharose and Superdex 75 gel filtration column to purify the allergen. Specific IgE against purified protein was estimated via ELISA and immunoblot. The protein was subjected to mass spectrometric analysis. Glycan characterization was performed by Schiff staining and lectin binding assay followed by deglycosylation studies. The functional activity of the purified protein was evaluated by the basophil activation test. Cross-reactivity was assessed by inhibition studies with legume extracts. RESULTS: A 35 kDa protein was purified and showed 75% IgE reactivity with the patients' sera by ELISA and immunoblot. Glycan characterization of protein demonstrated the presence of terminal glucose and mannose residues. A reduction of 40% and 27% in IgE binding was observed upon chemical and enzymatic deglycosylation of the protein, respectively. The glycoprotein allergen upregulates the expression of CD203c on basophils which was significantly reduced upon deglycosylation, signifying its biological ability to activate the effector cells. The identified protein shared significant homology with Lup an 1 from the lupine bean. Immunoblot inhibition studies of the purified allergen with legume extracts underlined high cross-reactive potential. Complete inhibition was observed with peanut and common bean, while up to 70% inhibition was demonstrated with soy, black gram, chickpea, and lima bean. CONCLUSION: A 35 kDa vicilin-like major allergen was isolated from P. juliflora. The protein possesses glycan moieties crucial for IgE binding and basophil activation. Furthermore, the purified protein shows homology with Lup an 1 and exhibits cross-reactivity with common edible legume proteins.

Bioinformatic and immunological investigation of Per a 5 (delta class GST) allergen from Periplaneta americana.

INTRODUCTION: GSTs are multifunctional enzymes involved in cellular detoxification and present as potent allergens in several sources. Present study investigates allergenic relevance of GST from P. americana and determine its cross reactive potential with other indoor allergen sources. METHODS: Computational analysis with FASTA and ConSurf webserver was performed to determine potentially cross reactive allergens. Further, Per a 5 gene was cloned in pET 22b+ vector and expressed in E.coli BL21 cells and the rPer a 5 protein was purified using Ni-NTA affinity chromatography. Enzymatic activity of rPer a 5 was assessed using CDNB and cumene hydroperoxide. ELISA and immunoblot were performed using cockroach hypersensitive patient's sera. Functional activity of rPer a 5 was evaluated by basophil activation test. Inhibition studies were carried out with D. pteronyssinus, A. alternata and C. lunata extracts. RESULTS: Per a 5 demonstrates highest sequence similarity with delta class GST of Blattella germanica (94.9%). It also exhibits significant sequence similarity (50-58%) with mite, fungal and helminth allergenic GSTs. ConSurf analysis reveals high degree of evolutionary similarity in N terminal region of Per a 5, especially at GST dimerization interface. The purified rPer a 5 protein resolved at 27 kDa on SDS-PAGE. The rPer a 5 protein exhibits GST activity and possess upto 65% immunoreactivity with cockroach hypersensitive patient's sera in ELISA and immunoblot. It upregulates expression of CD203c on basophils signifying its biological ability to activate effector cells. rPer a 5 significantly inhibits corresponding GSTs in P. americana, D. pteronyssinus, A. alternata and C. lunata with EC50 values of 15.5 ng. 38.38 ng, 41.4 ng and 61.66 ng, respectively. CONCLUSION: Recombinant delta class GST of P. americana is a clinically relevant allergen showing upto 65% immunoreactivity with hypersensitive patient's sera. Per a 5 GST allergen showed phylogenetic similarity with dust mite, fungal and birch allergens thereby demonstrating allergen cross reactivity.

Clinical practice guidelines 2019: Indian consensus-based recommendations on influenza vaccination in adults.

Influenza, a common cause of acute respiratory infections, is an important health problem worldwide, including in India. Influenza is associated with several complications; people with comorbidities and the elderly are at a higher risk for such complications. Moreover, the influenza virus constantly changes genetically, thereby worsening therapeutic outcomes. Vaccination is an effective measure for the prevention of influenza. Despite the availability of global guidelines on influenza vaccination in adults, country-specific guidelines based on regional variation in disease burden are required for better disease management in India. With this aim, the Indian Chest Society and National College of Chest Physicians of India jointly conducted an expert meeting in January 2019. The discussion was aimed at delineating evidence-based recommendations on adult influenza vaccination in India. The present article discusses expert recommendations on clinical practice guidelines to be followed in India for adult influenza vaccination, for better management of the disease burden.

Clinical practice guidelines 2019: Indian consensus-based recommendations on pneumococcal vaccination for adults.

Similar to the global scenario, pneumococcal diseases are a significant health concern in India. Pneumococcal diseases occur frequently among adults and are largely preventable through vaccines. Globally, several guidelines and recommendations are available for pneumococcal vaccination in adults. However, owing to wide variations in the disease burden, regulatory landscape, and health-care system in India, such global guidelines cannot be unconditionally implemented throughout the country. To address these gaps, the Indian Chest Society and National College of Chest Physicians of India jointly conducted an expert meeting in January 2019. The aim of the discussion was to lay down specific evidence-based recommendations on adult pneumococcal vaccination for the country, with a view to further ameliorate the disease burden in the country. This article presents an overview of the closed-door discussion by the expert members on clinical practice guidelines to be followed for adult pneumococcal vaccination in India.

Joint Indian Chest Society-National College of Chest Physicians (India) guidelines for spirometry.

Although a simple and useful pulmonary function test, spirometry remains underutilized in India. The Indian Chest Society and National College of Chest Physicians (India) jointly supported an expert group to provide recommendations for spirometry in India. Based on a scientific grading of available published evidence, as well as other international recommendations, we propose a consensus statement for planning, performing and interpreting spirometry in a systematic manner across all levels of healthcare in India. We stress the use of standard equipment, and the need for quality control, to optimize testing. Important technical requirements for patient selection, and proper conduct of the vital capacity maneuver, are outlined. A brief algorithm to interpret and report spirometric data using minimal and most important variables is presented. The use of statistically valid lower limits of normality during interpretation is emphasized, and a listing of Indian reference equations is provided for this purpose. Other important issues such as peak expiratory flow, bronchodilator reversibility testing, and technician training are also discussed. We hope that this document will improve use of spirometry in a standardized fashion across diverse settings in India.

Guidelines for diagnostic flexible bronchoscopy in adults: Joint Indian Chest Society/National College of chest physicians (I)/Indian association for bronchology recommendations.

Flexible bronchoscopy (FB) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. However, bronchoscopy practices vary widely across India and worldwide. The three major respiratory organizations of the country supported a national-level expert group that formulated a comprehensive guideline document for FB based on a detailed appraisal of available evidence. These guidelines are an attempt to provide the bronchoscopist with the most scientifically sound as well as practical approach of bronchoscopy. It involved framing appropriate questions, review and critical appraisal of the relevant literature and reaching a recommendation by the expert groups. The guidelines cover major areas in basic bronchoscopy including (but not limited to), indications for procedure, patient preparation, various sampling procedures, bronchoscopy in the ICU setting, equipment care, and training issues. The target audience is respiratory physicians working in India and well as other parts of the world. It is hoped that this document would serve as a complete reference guide for all pulmonary physicians performing or desiring to learn the technique of flexible bronchoscopy.

Immunogenic peptides: B & T Cell Epitopes of Per a 10 Allergen of Periplaneta americana.

Mapping of B and T cell epitopes of an allergen can be utilised in the development of alternative therapeutic modalities and diagnostics. The present study was aimed to identify B and T cell epitopes of Per a 10, a major cockroach allergen, by computational tools and subsequent validation by in vitro experiments. Per a 10 three-dimensional structure was homology modelled using structure of anionic trypsin from pacific chum salmon as a template. Seven B cell epitopes (B-P1 to B-P7) were predicted by sequence and structure based methods. Three T cell epitopes (T-P8 to T-P10) were predicted by binding score and inhibitory concentration dependent prediction tools. Predicted epitopes were synthesized and biological activity was assessed by ELISA, ELISA inhibition and PBMC proliferation assays. B cell peptides B-P5, B-P6 and B-P7 showed significantly high IgE binding with pooled and individual cockroach hypersensitive patients' sera while the T cell peptides did not show IgE binding. ELISA inhibition was performed to determine the potency of the predicted peptides. Fifty nanogram of peptide B-P7 was required for 50% IgE binding inhibition of surface bound Per a 10 whereas seventy five nanogram and ninety nanogram of B-P5 and B-P6 were required for the same respectively. Upon stimulation with T-P8 and T-P10 peptides, PBMCs from cockroach allergic patients' (n = 15) showed significant lymphocyte proliferation and induced IL-4 and IL-5 cytokine release in the culture supernatant demonstrating Th2 dominant cell mediated response of predicted T cell peptides. In conclusion, Per a 10 3-D structure obtained by homology modelling was used to identify B and T cell epitopes, followed by in vitro validation. The identified peptides can be potentially used in designing diagnostics and therapies for cockroach allergy.

Medication education program for Indian children with asthma: A feasibility stud.

OBJECTIVE: It is postulated that children with asthma who receive an interactive, comprehensive, culturally relevant education program would improve their asthma knowledge (AK), asthma control, and adherence compared with children receiving usual care. The aim of this study was to develop, implement, and evaluate the efficacy of a culturally relevant asthma education intervention for children with asthma and their parents in India. METHODS: Children with asthma (7-12 years) and their parents were recruited from an outpatient clinic in a Chest Diseases Hospital in New Delhi, and were randomly assigned to either an intervention or usual care group. At baseline, outcome data collected included pediatric asthma caregiver quality of life (PACQL, primary outcome), AK, asthma control, adherence, inhaler technique, action plan ownership, and goal achievement. These data were collected again at 1 and 6 months after baseline. Outcomes were compared within and between groups using ANOVA techniques. RESULTS: Forty parent-child pairs were recruited. Of these, 24 pairs of children with asthma and their parents received the educational intervention. The PACQL significantly improved from baseline to 6 months in the intervention (5.87 ± 0.94-7.00 ± 0.03) versus the usual care group (5.90 ± 0.52-6.34 ± 0.56) (P < 0.001). Other outcomes such as the parents' and child's AK, child's asthma control and inhaler technique were significantly improved in the intervention group across the study. All the participants possessed a written asthma action plan at the end of the intervention. Eighty-five goals were set by children with asthma across all the visits and were achieved by completion. CONCLUSION: An asthma educator delivered interactive program simultaneously involving children with asthma and their parents, improved quality of life, empowered and promoted better self-management skills.

In vitro assessment of allergenicity features and localization of probable IgE binding regions.

Rice is cultivated as a staple grain crop in many countries, especially in Asia. In the present study, recombinant rice chitinase was expressed, purified and characterized by in silico and immunobiochemical methods. Rice chitinase was affinity purified and it resolved at 24 kDa on SDS-PAGE. Purified protein was analyzed for pepsin resistance, heat stability, and IgE binding using atopic patients' sera. Chitinase was resistant to pepsin digestion and heat treatment at 90 °C for 1 h. It showed significant IgE binding with 7 of 110 patients' sera positive to different food allergens. Homology modeled 3D structure of rice chitinase was used for B cell epitope prediction. In silico predicted B cell peptides were assessed for IgE binding by ELISA using food allergic patients' sera, epitope RC2 showed IgE binding comparable to chitinase. In conclusion, chitinase was identified as a potential allergen and may share cross reactive epitopes with food allergens.

Antimicrobial drug prescribing patterns for community-acquired pneumonia in hospitalized patients: A retrospective pilot study from New Delhi, India.

OBJECTIVE: The objective of this study was to determine patterns and frequency of antimicrobial drug use among hospitalized patients with community-acquired pneumonia (CAP). METHODOLOGY: A retrospective 5 years (April 2007-March 2012) detailed medical record review of patients diagnosed with CAP and discharged to home from Non-Intensive Care Unit respiratory medicine wards of two public hospitals in Delhi. RESULTS: A total of 261 medical records were analyzed. Over the 5 years, 82.0% (2007-08), 78.6% (2008-09), 59.5% (2009-10), 64.7% (2010-11), and 67.8% (2011-12) patients were prescribed two antimicrobials. In the last two study years, the proportion of patients receiving three antimicrobials increased (from 2.0% to 26.5% and 28.8%), while the proportion receiving monotherapy decreased (from 16.0% to 8.8% and 3.4%). In accordance with guidelines, beta-lactams and macrolides were the two most frequently prescribed antimicrobials (34.1%). However, newer generation beta-lactams were prescribed. A total of 37 patients were prescribed beta-lactam-tazobactam combination preparations. Overall, beta-lactams constituted more than 40% of prescriptions while macrolides were the second most prescribed class. Cephalosporin prescriptions significantly increased (P < 0.01) and penicillin prescriptions significantly decreased over study periods. The prescription of fluoroquinolones also decreased (21.5-6.0%, P < 0.01) and aminoglycoside prescription ranged from 9.7% to 16.4%, over 5 years. Reasons for prescribing three antimicrobials, use of aminoglycosides, or higher-end/reserve antibiotics were not mentioned in the medical records. There were no hospital-specific guidelines for doctors to follow in the treatment of CAP. CONCLUSIONS: These findings suggest the need for implementing antimicrobial treatment guidelines. Adequate documentation and monitoring of antibiotic use for feedback are also lacking. An antimicrobial stewardship program may offer the most comprehensive solution for appropriate use of antimicrobials.

DC type 2 polarization depends on both the allergic status of the individual and protease activity of Per a 10.

Cockroach proteases are important risk factors for asthma development in predisposed individuals. In the present study, effect of allergic status of patients on DCs polarization in response to protease allergen Per a 10 was investigated. Cockroach-allergic, other-allergic patients and healthy individuals were selected following the guidelines of ATS/ARIA. Monocyte-derived dendritic cells (DCs) were generated from the selected individuals and stimulated with Per a 10. Flow cytometric analysis showed a significantly high expression of CD80 and CD86 on DCs from cockroach-allergic patients after Per a 10 stimulation as compared to healthy individuals or other-allergic patients (P<0.05). Per a 10 induced comparable level of CD83 expression on DCs from all the 3 groups, showing it was irrespective of the allergic status. CD40 expression was significantly low (P<0.05) on the DCs from cockroach-allergic patients as compared to healthy individuals or other-allergic patients. Further, proteolytically active Per a 10 induced lower CD40 expression on DCs than the heat-inactivated Per a 10 (P<0.05) indicating role of protease activity in the generation of an immune response. The sCD40 level in active Per a 10 stimulated DC cultures was significantly higher than in heat-inactivated Per a 10 (P<0.05). There was two-fold decrease (P<0.05) in IL-12 production by active Per a 10-stimulated DCs than heat-inactivated Per a 10-stimulated DCs. Per a 10-stimulated DCs from cockroach-allergic patients secreted high levels of IL-5, IL-6, TNF-α than that from healthy individuals or other-allergic patients (P<0.05). Furthermore, Per a 10-stimulated DCs from cockroach-allergic patients induced increased secretions of IL-4, IL-5, IL-6, TNF-α and low IL-12 by T cells as compared to those from other groups (P<0.05). Thus, in presence of Per a 10 allergen, polarization of DCs shifts toward type 2 in cockroach-allergic patients but not in the healthy individuals or other-allergic patients. In conclusion, both allergic status of the individual and protease activity of Per a 10 are important parameters that participate in DCs polarization.

Per a 10 protease activity modulates CD40 expression on dendritic cell surface by nuclear factor-kappaB pathway.

Serine protease activity of Per a 10 from Periplaneta americana modulates dendritic cell (DC) functions by a mechanism(s) that remains unclear. In the present study, Per a 10 protease activity on CD40 expression and downstream signalling was evaluated in DCs. Monocyte-derived DCs from cockroach-allergic patients were treated with proteolytically active/heat-inactivated Per a 10. Stimulation with active Per a 10 demonstrated low CD40 expression on DCs surface (P < 0·05), while enhanced soluble CD40 level in the culture supernatant (P < 0·05) compared to the heat-inactivated Per a 10, suggesting cleavage of CD40. Per a 10 activity reduced the interleukin (IL)-12 and interferon (IFN)-γ secretion by DCs (P < 0·05) compared to heat-inactivated Per a 10, indicating that low CD40 expression is associated with low levels of IL-12 secretion. Active Per a 10 stimulation caused low nuclear factor-kappa B (NF-κB) activation in DCs compared to heat-inactivated Per a 10. Inhibition of the NF-κB pathway suppressed the CD40 expression and IL-12 secretion by DCs, further indicating that NF-κB is required for CD40 up-regulation. CD40 expression activated the tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6), thereby suggesting its involvement in NF-κB activation. Protease activity of Per a 10 induced p38 mitogen-activated protein kinase (MAPK) activation that showed no significant effect on CD40 expression by DCs. However, inhibiting p38 MAPK or NF-κB suppressed the secretion of IL-12, IFN-γ, IL-6 and TNF-α by DCs. Such DCs further reduced the secretion of IL-4, IL-6, IL-12 and TNF-α by CD4(+) T cells. In conclusion, protease activity of Per a 10 reduces CD40 expression on DCs. CD40 down-regulation leads to low NF-κB levels, thereby modulating DC-mediated immune responses.

Immunotherapy with B cell epitopes ameliorates inflammatory responses in Balb/c mice.

Osmotin, a protein from the pathogenesis-related family (PR-5), has been identified as an allergen based on in-silico and in-vitro studies. In the present study, three B cell epitopes of osmotin with single and double amino acid modifications were studied for immunotherapy in a murine model. The single-modification peptides (P-1-1, P-2-1 and P-3-1) and double-modification peptides (P-1-2, P-2-2 and P-3-2) showed significantly lower immunoglobulin (Ig)E binding with patients' sera compared to osmotin (P < 0·01). These peptides showed reduced IgE binding compared to the unmodified peptides (B cell epitopes) P-1, P-2 and P-3. Among the modified peptides, P-2-1, P-3-1, P-2-2 and P-3-2 showed significant reduction in IgE binding and were used for immunotherapy in mice. The sera of mice group treated with peptides showed a significant increase in IgG2a level and a significant decrease in IgE and IgG1 levels (P < 0·05). The mice that received peptide immunotherapy showed a shift from a T helper type 2 (Th2) to Th1 type where interferon (IFN)-γ and interleukin (IL)-10 levels were elevated, with a significant increase in groups treated with peptides P-3-1 and P-3-2 (P < 0·05). There was a reduction in the IL-4 and IL-5 levels in bronchoalveolar lavage fluid (BALF) in the peptide-treated mice groups. Total cell count and eosinophil count in BALF of the peptide-treated groups was also reduced compared to the phosphate-buffered saline (PBS)-treated group. Lung histology showed a significant reduction in cellular infiltrate in mice treated with P-2-2 and P-3-2 compared to PBS. In conclusion, peptides P-2-2 and P-3-2 lowered inflammatory responses and induced a Th1 response in mice.

An Unusual Cause of a Pulmonary Mass: Actinomycosis.

We present the case of a 62-year-old male with chronic obstructive pulmonary disease and poorly controlled diabetes mellitus who presented with haemoptysis. A radiograph of the chest showed a right lower parahilar opacity which on the contrast enhanced computed tomography was seen to be an irregular, spiculated mass localised to the middle lobe. Considering malignancy as the most probable diagnosis, a bronchoscopic endobronchial biopsy was performed which surprisingly established pulmonary actinomycosis as the diagnosis. The patient was successfully managed with amoxicillin and clavulanic acid and glycaemic control.

Guidelines for Diagnosis and Management of Bronchial Asthma: Joint Recommendations of National College of Chest Physicians (India) and Indian Chest Society.

Bronchial asthma is an important public health problem in India with significant morbidity. Several international guidelines for diagnosis and management of asthma are available, however there is a need for country-specific guidelines due to vast differences in availability and affordability of health-care facilities across the globe. The Indian Chest Society (ICS) and the National College of Chest Physicians (NCCP) of India have collaborated to develop evidence-based guidelines with an aim to assist physicians at all levels of health-care in diagnosis and management of asthma in a scientific manner. Besides a systematic review of the literature, Indian studies were specifically analysed to arrive at simple and practical recommendations. The evidence is presented under these five headings: (1) definitions, epidemiology and impact, (2) diagnosis, (3) pharmacologic management of stable disease, (4) management of acute exacerbations, and (5) non-pharmacologic management and special situations. The modified grade system was used for classifying the quality of evidence as 1, 2, 3, or usual practice point (UPP). The strength of recommendation was graded as A or B depending upon the level of evidence.