Publications

BACKGROUND

Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk.

METHODS

We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function.

RESULTS

RSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted.

CONCLUSIONS

A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population.

BACKGROUND

Dehydration due to diarrhoea is a leading cause of child death worldwide, yet no clinical tools for assessing dehydration have been validated in resource-limited settings. The Dehydration: Assessing Kids Accurately (DHAKA) score was derived for assessing dehydration in children with diarrhoea in a low-income country setting. In this study, we aimed to externally validate the DHAKA score in a new population of children and compare its accuracy and reliability to the current Integrated Management of Childhood Illness (IMCI) algorithm.

METHODS

DHAKA was a prospective cohort study done in children younger than 60 months presenting to the International Centre for Diarrhoeal Disease Research, Bangladesh, with acute diarrhoea (defined by WHO as three or more loose stools per day for less than 14 days). Local nurses assessed children and classified their dehydration status using both the DHAKA score and the IMCI algorithm. Serial weights were obtained and dehydration status was established by percentage weight change with rehydration. We did regression analyses to validate the DHAKA score and compared the accuracy and reliability of the DHAKA score and IMCI algorithm with receiver operator characteristic (ROC) curves and the weighted κ statistic. This study was registered with ClinicalTrials.gov, number NCT02007733.

FINDINGS

Between March 22, 2015, and May 15, 2015, 496 patients were included in our primary analyses. On the basis of our criterion standard, 242 (49%) of 496 children had no dehydration, 184 (37%) of 496 had some dehydration, and 70 (14%) of 496 had severe dehydration. In multivariable regression analyses, each 1-point increase in the DHAKA score predicted an increase of 0·6% in the percentage dehydration of the child and increased the odds of both some and severe dehydration by a factor of 1·4. Both the accuracy and reliability of the DHAKA score were significantly greater than those of the IMCI algorithm.

INTERPRETATION

The DHAKA score is the first clinical tool for assessing dehydration in children with acute diarrhoea to be externally validated in a low-income country. Further validation studies in a diverse range of settings and paediatric populations are warranted.

FUNDING

National Institutes of Health Fogarty International Center.

Black men who have sex with men in the USA face disproportionate incidence rates of HIV. This paper presents findings from an ethnographic study conducted in New York City that explored the structural and socio-cultural factors shaping men's sexual relationships with the goal of furthering understandings of their HIV-related vulnerability. Methods included participant observation and in-depth interviews with 31 Black men who have sex with men (three times each) and 17 key informants. We found that HIV vulnerability is perceived as produced through structural inequalities including economic insecurity, housing instability, and stigma and discrimination. The theoretical concepts of social risk, intersectional stigma, and the social production of space are offered as lenses through which to analyse how structural inequalities shape HIV vulnerability. We found that social risk shaped HIV vulnerability by influencing men's decisions in four domains: 1) where to find sexual partners, 2) where to engage in sexual relationships, 3) what kinds of relationships to seek, and 4) whether to carry and to use condoms. Advancing conceptualisations of social risk, we show that intersectional stigma and the social production of space are key processes through which social risk generates HIV vulnerability among Black men who have sex with men.