Preventive allergen immunotherapy with inhalant allergens in children.

The efficacy and safety of preventive allergen immunotherapy (pAIT) in children are currently under investigation. Here, we provide an overview of pAIT with respiratory allergens concerning the prevention of new sensitizations, allergic disease onset and progression as well as further immunomodulatory effects. Three databases were searched for clinical pAIT studies in children. Selected publications were reviewed for preventive outcomes according to prevention level (primary, secondary, and tertiary), allergen type, administration route, dose, and treatment duration. The primary prevention approach appears safe but showed no allergen-specific effect on new sensitizations. Secondary prevention seems feasible and may induce regulatory T cell-mediated immunotolerance. The number of studies at these prevention levels is limited. Tertiary prevention with grass and/or tree pollen-based pAIT has shown efficacy in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Data on tertiary pAIT with house dust mites and other allergen types are inconclusive. Subcutaneous and sublingual routes appear similarly effective, but head-to-head comparative paediatric studies are scarce. Additionally, there are fewer placebo-controlled studies. Nevertheless, immunomodulatory outcomes of pAIT are encouraging. Currently, limited but favourably suggestive evidence is available for preventing respiratory allergic diseases in children by pAIT. Primary and secondary prevention have potential and warrant further investigation through well-designed studies.

Limited role of children in transmission of SARS-CoV-2 virus in households-Immunological analysis of 26 familial clusters.

BACKGROUND: The impact of children on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains uncertain. This study provides an insight into distinct patterns of SARS-CoV-2 household transmission in case of pediatric and adult index cases as well as age-dependent susceptibility to SARS-CoV-2 infection. METHODS: Immune analysis, medical interviewing, and contact tracing of 26 families with confirmed SARS-CoV-2 infection cases have been conducted. Blood samples were analyzed serologically with the use of a SARS-CoV-2-specific IgG assay and virus neutralization test (VNT). Uni- and multivariable linear regression and mixed effect logistic regression models were used to describe potential risk factors for higher contagiousness and susceptibility to SARS-CoV-2 infection. RESULTS: SARS-CoV-2 infection could be confirmed in 67 of 124 family members. Fourteen children and 11 adults could be defined as index cases in their households. Forty of 82 exposed family members were defined as secondarily infected. The mean secondary attack rate in households was 0.48 and was significantly higher in households with adult than with pediatric index cases (0.85 vs 0.19; p < 0.0001). The age (grouped into child and adult) of index case, severity of disease, and occurrence of lower respiratory symptoms in index cases were significantly associated with secondary transmission rates in households. Children seem to be equally susceptible to acquire a SARS-CoV-2 infection as adults, but they suffer milder courses of the disease or remain asymptomatic. CONCLUSION: SARS-CoV-2 transmission from infected children to other household members occurred rarely in the first wave of the pandemic, despite close physical contact and the lack of hygienic measures.

Long-Lived Immunity in SARS-CoV-2-Recovered Children and Its Neutralizing Capacity Against Omicron.

SARS-CoV-2 infection is effectively controlled by humoral and cellular immune responses. However, the durability of immunity in children as well as the ability to neutralize variants of concern are unclear. Here, we assessed T cell and antibody responses in a longitudinal cohort of children after asymptomatic or mild COVID-19 over a 12-month period. Antigen-specific CD4 T cells remained stable over time, while CD8 T cells declined. SARS-CoV-2 infection induced long-lived neutralizing antibodies against ancestral SARS-CoV-2 (D614G isolate), but with poor cross-neutralization of omicron. Importantly, recall responses to vaccination in children with pre-existing immunity yielded neutralizing antibody activities against D614G and omicron BA.1 and BA.2 variants that were 3.9-fold, 9.9-fold and 14-fold higher than primary vaccine responses in seronegative children. Together, our findings demonstrate that SARS-CoV-2 infection in children induces robust memory T cells and antibodies that persist for more than 12 months, but lack neutralizing activity against omicron. Vaccination of pre-immune children, however, substantially improves the omicron-neutralizing capacity.

Natural Killer Cells Contribute to Pathogenesis of Severe Alcoholic Hepatitis by Inducing Lysis of Endothelial Progenitor Cells.

BACKGROUND: Endothelial progenitor cells (EPCs) help in neovascularization and endothelial repair during injury. Patients with cirrhosis show increased number and function of EPCs in circulation. METHODS: Since natural killer (NK) cells regulate EPCs, we investigated the relationship between the 2 in alcoholic cirrhosis (AC, n = 50) and severe alcoholic hepatitis (SAH, n = 18) patients and compared with nonalcoholic cirrhosis (n = 15) and healthy controls (HC, n = 30). Levels of systemic inflammatory cytokines were measured, and coculture assays were performed between EPCs and NK cells in contact-dependent and contact-independent manner. NK cell-mediated killing of EPCs was evaluated, and expression of receptors including fractalkine (FKN) on EPCs and its cognate receptor CX3CR1 on NK cells was studied by RT-PCR assays. RESULTS: Patients with SAH had higher regulated on activation, normal T cell expressed and secreted (RANTES) (p = 0.01), vascular endothelial growth factor (VEGF) (p = 0.04), IL-1ß (p = 0.04), and IL-6 (p = 0.00) growth factors and proinflammatory cytokines as compared to AC and HC. Distinct populations of CD31+ CD34+ EPCs with low and high expression of CD45 were significantly lower in SAH than HC (CD45low , p = 0.03; CD45hi , p = 0.04) and AC (CD45low , p = 0.05; CD45hi , p = 0.02). SAH patients, however, showed increased functional capacity of EPCs including colony formation and LDL uptake. NK cells were reduced in SAH compared with AC (p = 0.002), however with higher granzyme ability (p < 0.001 and p = 0.04, respectively). In SAH, EPC-NK cell interaction assays showed that NK cells lysed the EPCs in both contact-dependent and contact-independent assays. Expression of interaction receptor CX3CR1 was significantly higher on NK cells (p = 0.0005), while its cognate receptor, FKN, was increased on EPCs in SAH patients as compared to HC (p = 0.0055). CONCLUSION: We conclude that in SAH, NK cells induce killing of EPCs via CX3CR1/FKN axis that may be one of the key events contributing to disease severity and proinflammatory responses in SAH.

A randomized, double-blind, placebo-controlled trial of ormeloxifene in breast pain and nodularity.

BACKGROUND: Breast pain and non-discrete breast nodularity are common in women. METHODS: We did a randomized, double-blind, placebocontrolled trial of oral ormeloxifene 30 mg, a selective oestrogen receptor modulator (SERM) or placebo twice a week for 3 months in 20-50-year-old women with breast pain with or without lumpiness. Women with a discrete benign lump or cancer were excluded from the study. Serial assessments of pain on a visual analogue scale and nodularity grade on a 5-point ordinal Lucknow-Cardiff scale were done. A total of 151 patients were randomly allocated to two interventions using a block size of 4. RESULTS: Of the 151 patients, 121 (active 57, placebo 64) were available for efficacy analysis. The mean pain level showed a systematic downward trend over five visits (F=105.23, p<0.0001) that significantly reduced in the active group compared to that in the placebo group (F=18.66, p<0.0001). The patterns of variation in pain over time for the individual groups differ from the overall mean pattern for the two groups and thus from one another (F=44.43, p<0.0001). Cumulative frequencies of breast nodularity grades during successive visits showed significant improvement (p=0.001) compared to placebo at the end of the third month. The effect of the active drug persisted till the completion (6 months) of treatment (p<0.001). At the last visit, 93.3% of women in the active group had grade 2 or lower nodularity as compared to 71.1% in the placebo group. Oligomenorrhoea alone was reported by 12 patients. CONCLUSION: Ormeloxifene showed significant efficacy for treating breast pain and nodularity.

Human sodium iodide symporter (hNIS) in fibroadenoma breast--a immunohistochemical study.

Human sodium iodide symporter (hNIS), responsible for the active transport of iodine is an integral plasma membrane glycoprotein present in the thyroid cells and extrathyroid tissues like breast and salivary glands. If its functional form is unequivocally shown in benign or malignant breast tissues, then it may serve as a basis for diagnosis and treatment using radioactive iodine. With an aim to analyze the hNIS expression in a distinct benign breast condition of fibroadenoma, biopsy proven fibroadenoma tissues, normal non-lactating breast tissue and biopsy proven infiltrating duct carcinoma tissues were examined for hNIS expression using immunohistochemistry. Out of 20 biopsy proven fibroadenoma tissues, 19 (95%) showed positivity for hNIS protein and only one was negative. Of these 10% were mildly positive, 50% cases were moderately positive and 35% showed intense positivity. None of the control tissue obtained from reduction mammoplasty specimens or normal breast tissues samples (5 cms away from the tumor) were positive, hNIS was also intensely positive in 9 out of 10 (90%) infiltrating duct carcinoma tissues and moderately positive in one case. These preliminary results show that hNIS was present in high frequency as demonstrated by immunohistochemistry in fibroadenoma breast.

Tobacco use in Northern India-Part 1: The detailed habit.

BACKGROUND: The finite details of tobacco consumption practices in north Indian population are hitherto not well described. This study depicts the modes of tobacco use, their relative frequency, demographic and psychosocial determinants. MATERIALS AND METHODS: Random stratified sampling from the list of blocks, villages and urban localities was done. The study was community-based house-to-house survey using interview schedule. RESULTS: There were 1607 tobacco users: 1399 male and 208 female; 1195 urban and 412 rural. Single mode of tobacco use was reported by 769 (47.85%). Chewing tobacco was prevalent in 511 (31.80%), smoking in 258 (16.55%) subjects and majority 838 (52.15%) had consistent multiple habit of smoking and chewing. Of the 10 preparations of tobacco use, the 'top 5' ranked as tobacco-betel, gutka, cigarette, bidi and khaini. Gutka consumption was significantly higher between age group of 25 years and 55 years (χ(2) = 17.2; P<0.000). Majority of users, 576 (35.84%), started tobacco before 25 years of age and about a fifth, 439 (27.32%) before 18 years. Men significantly used tobacco more than women (χ(2) = 73.2; P<0.000). Women (χ(2) = 73.2; P<0.000) preferred smokeless tobacco and perceived social barrier for smoking. CONCLUSION: Multiple or overlapping tobacco practices and other substances abuse were documented in Lucknow, the capital city of the most populous state Uttar Pradesh where chewing tobacco was the commonest as opposed to smoking.

Visual analogue scale for assessing breast nodularity in non-discrete lumpy breasts: the Lucknow-Cardiff breast nodularity scale.

BACKGROUND: Objective measurement of benign non-discrete lumpy breasts is not performed routinely that would lead to disease measurement, inter-physician communication, therapeutic response assessment and a normative function of reducing unnecessary biopsies. A schematic 5-point ordinal visual analogue scale was developed. METHODS: Two blinded experienced clinicians graded breast nodularity on a pre-determined five point analogue scale (grades 0-4) to determine its inter-observer reliability after its face validity that excluded inflammatory, nipple, areola and discrete lump problems. RESULTS: 784 Women (hospital 384; community 400) aged between 20 and 70 years (mean 31.9) underwent physical breast examination by 2 experienced clinicians. Inter-observer matched nodularity grading in women attending hospital were Grade 0 in 123 (32.03%), grade 1 in 67 (17.44%), grade 2 in 54 (14.06%), grade 3 in 52 (13.54%) and grade 4 in 23 (5.99%) and in community it was grade 0 in 172 (43%), grade 1 in 88 (22%), grade 2 in 60 (15%), grade 3 in 28 (7%) and grade 4 in 14 (3.5%) women. There was very good agreement (kappa = 0.7798) across all grades in hospital subjects and excellent agreement (kappa = 0.8659) in community subjects. Both estimates of kappa coefficients were highly significant from population kappa coefficient of zero (p < 0.001). Overall, 1/3rd normal women have absolutely smooth textured breasts. CONCLUSION: User-friendly tool developed for objective evaluation of non-discrete lumpy breasts showed excellent reliability and validity. This tool should be useful for clinical drug trials in benign breast disorders and for wide routine clinical recording of patients.

A study of knowledge, attitude and practice of hospital consultants, resident doctors and private practitioners with regard to pre-hospital and emergency care in Lucknow.

BACKGROUND: Burden of death and disability resulting from lack of emergency medical system (EMS) and emergency care is very high in low and middle income countries (LMIC). AIM: To study the knowledge, attitudes and practices of pre-hospital care and emergency services among health care providers of Lucknow SETTING AND DESIGN: Cross-sectional survey, 200 residents, 104 hospital consultants and 108 private practitioners MATERIAL AND METHODS: A close ended, self administered questionnaire based on 5-point Likert scale with 30 items of knowledge, attitude and practice of pre-hospital and emergency care RESULTS: Median scores of knowledge (26/50), attitude (41/50) and practices (27/50) showed less than adequate knowledge and practices. However, a positive attitude was seen in all the 3 group of respondents i.e. resident doctors, hospital consultants and private practitioners. CONCLUSION: Lucknow is the capital city of Indian largest state - Uttar Pradesh with over 100 years of established medical education. The results of the study in this town are applicable to most developed cities in India. Lack of adequate knowledge and practices in emergency medical system (EMS) at Lucknow represent a dismal situation and require continuing medical education in this area.