Jaime Tarsi

Airway Remodeling Measured by Multidetector CT Is Increased in Severe Asthma and Correlates With Pathology

BACKGROUNDnTo prospectively apply an automated, quantitative three-dimensional approach to imaging and airway analysis to assess airway remodeling in asthma patients.nnnMETHODSnUsing quantitative software (Pulmonary Workstation, version 0.139; VIDA Diagnostics; Iowa City, IA) that enables quantitative airway segment measurements of low-dose, thin-section (0.625 to 1.25 mm), multidetector-row CT (MDCT) scans, we compared airway wall thickness (WT) and wall area (WA) in 123 subjects participating in a prospective multicenter cohort study, the National Institutes of Health Severe Asthma Research Program (patients with severe asthma, n = 63; patients with mild-to-moderate asthma, n = 35); and healthy subjects, n = 25). A subset of these subjects underwent fiberoptic bronchoscopy and endobronchial biopsies (n = 32). WT and WA measurements were corrected for total airway diameter and area: WT and WA, respectively.nnnRESULTSnSubjects with severe asthma had a significantly greater WT% than patients with mild-to-moderate asthma and healthy subjects (17.2 +/- 1.5 vs 16.5 +/- 1.6 [p = 0.014] and 16.3 +/- 1.2 [p = 0.031], respectively) and a greater WA percentage (WA%) compared to patients with mild-to-moderate asthma and healthy subjects (56.6 +/- 2.9 vs 54.7 +/- 3.3 [p = 0.005] and 54.6 +/- 2.4 [p = 0.003], respectively). Both WT% and WA% were inversely correlated with baseline FEV(1) percent predicted (r = -0.39, p < 0.0001 and r = -0.40, p < 0.0001, respectively) and positively correlated with response to a bronchodilator (r = 0.28, p = 0.002 and r = 0.35, p < 0.0001, respectively). The airway epithelial thickness measure on the biopsy sample correlated with WT% (r = 0.47; p = 0.007) and WA% (r = 0.52; p = 0.003). In the same individual, there is considerable regional heterogeneity in airway WT.nnnCONCLUSIONnPatients with severe asthma have thicker airway walls as measured on MDCT scan than do patients with mild asthma or healthy subjects, which correlates with pathologic measures of remodeling and the degree of airflow obstruction. MDCT scanning may be a useful technique for assessing airway remodeling in asthma patients, but overlap among the groups limits the diagnostic value in individual subjects.

Original ResearchAsthmaAirway Remodeling Measured by Multidetector CT Is Increased in Severe Asthma and Correlates With Pathology

BACKGROUNDnTo prospectively apply an automated, quantitative three-dimensional approach to imaging and airway analysis to assess airway remodeling in asthma patients.nnnMETHODSnUsing quantitative software (Pulmonary Workstation, version 0.139; VIDA Diagnostics; Iowa City, IA) that enables quantitative airway segment measurements of low-dose, thin-section (0.625 to 1.25 mm), multidetector-row CT (MDCT) scans, we compared airway wall thickness (WT) and wall area (WA) in 123 subjects participating in a prospective multicenter cohort study, the National Institutes of Health Severe Asthma Research Program (patients with severe asthma, n = 63; patients with mild-to-moderate asthma, n = 35); and healthy subjects, n = 25). A subset of these subjects underwent fiberoptic bronchoscopy and endobronchial biopsies (n = 32). WT and WA measurements were corrected for total airway diameter and area: WT and WA, respectively.nnnRESULTSnSubjects with severe asthma had a significantly greater WT% than patients with mild-to-moderate asthma and healthy subjects (17.2 +/- 1.5 vs 16.5 +/- 1.6 [p = 0.014] and 16.3 +/- 1.2 [p = 0.031], respectively) and a greater WA percentage (WA%) compared to patients with mild-to-moderate asthma and healthy subjects (56.6 +/- 2.9 vs 54.7 +/- 3.3 [p = 0.005] and 54.6 +/- 2.4 [p = 0.003], respectively). Both WT% and WA% were inversely correlated with baseline FEV(1) percent predicted (r = -0.39, p < 0.0001 and r = -0.40, p < 0.0001, respectively) and positively correlated with response to a bronchodilator (r = 0.28, p = 0.002 and r = 0.35, p < 0.0001, respectively). The airway epithelial thickness measure on the biopsy sample correlated with WT% (r = 0.47; p = 0.007) and WA% (r = 0.52; p = 0.003). In the same individual, there is considerable regional heterogeneity in airway WT.nnnCONCLUSIONnPatients with severe asthma have thicker airway walls as measured on MDCT scan than do patients with mild asthma or healthy subjects, which correlates with pathologic measures of remodeling and the degree of airflow obstruction. MDCT scanning may be a useful technique for assessing airway remodeling in asthma patients, but overlap among the groups limits the diagnostic value in individual subjects.

Longitudinal changes in airway remodeling and air trapping in severe asthma.

RATIONALE AND OBJECTIVESnPrevious cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aimed to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma.nnnMATERIALS AND METHODSnPhenotypic characterization and quantitative multidetector-row computed tomography (MDCT) of the chest were performed at baseline and ∼2.6xa0years later in 38 participants with asthma (severe nxa0=xa024 and mild-to-moderate nxa0=xa014) and nine normal controls from the Severe Asthma Research Program.nnnRESULTSnSubjects with severe asthma had a significant decline in postbronchodilator forced expiratory volume in 1 second percent (FEV1%) predicted over time (P < .001). Airway wall thickness measured by MDCT was increased at multiple airway generations in severe asthma compared to mild-to-moderate asthma (wall area percent [WA%]: Pxa0<xa0.05) and normals (Pxa0<xa0.05) at baseline and year 2. Over time, there was an increase in WA% and wall thickness percent (WT%) in all subjects (Pxa0=xa0.030 and .009, respectively) with no change in emphysema-like lung or air trapping. Baseline prebronchodilator FEV1% inversely correlated with WA% and WT% (both P < .05). In a multivariable regression model, baseline WA%, race, and health care utilization were predictors of subsequent airway remodeling.nnnCONCLUSIONSnSevere asthma subjects have a greater decline in lung function over time than normal subjects or those with mild-to-moderate asthma. MDCT provides a noninvasive measure of airway wall thickness that may predict subsequent airway remodeling.

Effect of Reducing Field of View on Multidetector Quantitative Computed Tomography Parameters of Airway Wall Thickness in Asthma

Objective We reduced the computed tomography (CT)–reconstructed field of view (FOV), increasing pixel density across airway structures and reducing partial volume effects, to determine whether this would improve accuracy of airway wall thickness quantification. Methods We performed CT imaging on a lung phantom and 29 participants. Images were reconstructed at 30-, 15-, and 10-cm FOV using a medium-smooth kernel. Cross-sectional airway dimensions were compared at each FOV with repeated-measures analysis of variance. Results Phantom measurements were more accurate when FOV decreased from 30 to 15 cm (P < 0.05). Decreasing FOV further to 10 cm did not significantly improve accuracy. Human airway measurements similarly decreased by decreasing FOV (P < 0.001). Percent changes in all measurements when reducing FOV from 30 to 15 cm were less than 3%. Conclusions Airway measurements at 30-cm FOV are near the limits of CT resolution using a medium-smooth kernel. Reducing reconstructed FOV would minimally increase sensitivity to detect differences in airway dimensions.

Associations between household air pollution and reduced lung function in women and children in rural southern India: ASSOCIATIONS BETWEEN HOUSEHOLD AIR POLLUTION AND LUNG FUNCTION

Half of the worlds population still relies on solid fuels to fulfill its energy needs for cooking and space heating, leading to high levels of household air pollution (HAP), adversely affecting human health and the environment. A cross‐sectional cohort study was conducted to investigate any associations between: (1) HAP metrics (mass concentration of particulate matter of aerodynamic size less than 2.5 μm (PM2.5), lung‐deposited surface area (LDSA) and carbon monoxide (CO)); (2) a range of household and socio‐demographic characteristics; and (3) lung function for women and children exposed daily to biomass cookstove emissions, in rural southern India. HAP measurements were collected inside the kitchen of 96 households, and pulmonary function tests were performed for the women and child in each enrolled household. Detailed questionnaires captured household characteristics, health histories and various socio‐demographic parameters. Simple linear and logistic regression analysis was performed to examine possible associations between the HAP metrics, lung function and all household/socio‐demographic variables. Obstructive lung defects (forced vital capacity (FVC) ≥ lower limit of normal (LLN) and forced expiratory volume in 1 second (FEV1)/FVC < LLN) were found in 8% of mothers and 9% of children, and restrictive defects (FVC < LLN and FEV1/FVC ≥ LLN) were found in 17% of mothers and 15% of children. A positive association between LDSA, included for the first time in this type of epidemiological study, and lung function was observed, indicating LDSA is a superior metric compared to PM2.5 to assess effects of PM on lung function. HAP demonstrated a moderate association with subnormal lung function in children. The results emphasize the need to look beyond mass‐based PM metrics to assess fully the association between HAP and lung function.

Exposure to Wood Smoke is Associated with Increased Risk of Asthma and Respiratory Symptoms in a Honduran Population

Background Exposure to environmental pollutants has been shown to be associated with asthma, but few studies have evaluated the effect of wood smoke on asthma and disease severity in a developing country, where use of stoves powered by solid fuels is a common practice. Objective In a population in Olancho, Honduras, we evaluated the association between cooking fuel, stove type and asthma. We also evaluated the effects of these factors on asthma symptoms, lung function, and atopy. Methods Participants with physician-diagnosed asthma (n = 597) and controls without asthma (n = 429) were recruited from the Olancho province in Honduras. Participants were interviewed using a questionnaire and their baseline pulmonary function was measured using spirometry. Results The prevalence of use of wood as a cooking fuel was 66.9% in the study population, of which 42.1% of participants used wood as their only fuel. Use of wood as a cooking fuel was more prevalent among households with lower income, lower maternal education, and less urbanization. The prevalence of use of an open wood stove as the primary cooking stove among participants with asthma was 6.2% higher (95% CI 0.8 – 11.7%, p = .02) than among healthy controls. In a multiple logistic regression model, we identified a significant association between use of an open wood stove and asthma (OR = 1.80, 95% CI = 1.17 - 2.78, p = 0.007), compared to the referent (electric) stove category. Among participants with asthma, we identified a significant association between use of wood as cooking fuel and increased daytime respiratory symptoms (OR = 1.46, CI: 1.01 – 2.58, p = 0.046) and nocturnal symptoms (OR = 2.51, CI: 1.04 - 2.62, p = 0.04), though not with pulmonary function. Among control participants without asthma, use of wood as cooking fuel was associated with atopy (OR = 1.94, CI = 1.14 – 3.33, p = 0.015) and cough (OR = 2.22, CI = 1.09 – 4.88, p = 0.04). Conclusions Use of an open wood stove for cooking in a developing country appears to be a significant risk factor for asthma and respiratory symptoms. Exposure to wood smoke may play a role in atopic sensitization and respiratory symptoms, leading to the development of obstructive lung disease in susceptible individuals.