Page 50 - Biennial Report 2018-20 Jun 2021

between asthma and COPD is the mode of inflammation: asthma is primarily driven by
eosinophils, while neutrophils play a key role in COPD. The obstruction in asthma is due to
bronchiolar constriction and mucus accumulation, while in COPD mucus accumulation plays a
greater role until late in the disease, when structural changes cause narrowing of airways.
Bronchodilators help in alleviating acute symptoms of asthma by counteracting the
bronchoconstriction but may not be useful in COPD.

Anurag Agrawal’s group had previously shown the importance of inositol polyphosphate 4-
phosphatase type I A (INPP4A) lipid phosphatase that negatively regulates the PI3K/Akt pathway
in asthma. Although INPP4A was known to localize inside cells, recent findings from this lab have
shown that INPP4A is secreted by airway epithelial cells. Extracellular INPP4A inhibits airway
inflammation and airway remodeling but was reduced in asthmatic patients and mouse models
of allergic airway inflammation. These findings led to the view that secretory INPP4A is a novel
"paracrine" layer of the intricate regulation of lung homeostasis.
A handheld forced oscillation device for improved detection and monitoring of airway disease
was developed at IGIB with support from USISTEF. The device for oscillometric measurements
of lung function incorporates time series analysis and pattern recognition for increased
sensitivity. Final certification-ready design was finalized, and five pieces were produced. The new
units were tested in an urban-rural cohort in Pune on people exposed to biomass combustion to
investigate the efficacy of the device in diagnosing early cases of COPD. Furthermore, lung
function sampling was performed in more than 1500 subjects of 10- 20 years of age from
multiple regions across India to explore the potential of diagnosing suboptimal lung
development in the Indian population. Application for CE certification was submitted. The final
design passed the biocompatibility (10993), ISO 18652 VOC, CO, CO2, Ozone and PM2.5 tests.
IEC 60601 EMC, general safety and home-use testing work are in progress by the independent
testing facility. To gain insights into the market acceptance, and customer validation of product
design, several public demonstrations were given to customers, pulmonologists, pediatricians
and respiratory therapists.

LOW LUNG-FUNCTION IN APPARENTLY HEALTHY INDIANS

A variety of factors like environment, lifestyle, pollution, malnutrition, reduced physical exercise
along with genetic factors influence low lung function in Indians. It was hypothesized that ‘quiet’
inflammatory small-airway pathology contributes to the observed low lung-function. To
understand whether non-obstructive low-lung-function in apparently healthy adult Indian
subjects in greater detail, the associations between low-lung-function, small airways
obstruction, lifestyle factors, environmental factors and host factors were modeled.

Studies were completed at 14 school sites, reflecting all major regions of India, for about 2600
children ranging from 10-18 years of age, living in generally comparable boarding schools, and
from similar socio-economic strata. Of these, biochemical measurements were performed for
about 1000 subjects. This data confirms that low lung function of Indians is accompanied by an
inflammatory state with inverse correlations between adjusted lung function and cytokines such
as IL-8, TNFα and IFN-gamma. More precisely, at any age, subjects having low lung function by

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