Bronchodilator Response Predicts Longitudinal Improvement in Small Airway Function in World Trade Center Dust Exposed Community Members

Abstract

The evolution of lung function, including assessment of small airways, was assessed in individuals enrolled in the World Trade Center Environmental Health Center (WTC-EHC). We hypothesized that a bronchodilator response at initial evaluation shown by spirometry or in small airways, as measured by forced oscillation technique (FOT), would be associated with improvement in large and small airway function over time. Standardized longitudinal assessment included pre and post bronchodilator (BD) spirometry (forced vital capacity, FVC; forced expiratory volume in 1 second, FEV1) and FOT (resistance at 5 Hz, R5; resistance at 5 minus 20 Hz, R5–20). Longitudinal changes were assessed using linear mixed-effects modelling with adjustment for potential confounders (median follow-up 2.86 years; 95% measurements within 4.9 years). Data demonstrated: (1) parallel improvement in airflow and volume measured by spirometry and small airway function (R5 and R5–20) measured by FOT; (2) the magnitude of longitudinal improvement was tightly linked to the initial BD response; and (3) longitudinal values for small airway function on FOT were similar to residual abnormality observed post BD at initial visit. These findings suggest presence of reversible and irreversible components of small airway injury that are identifiable at initial presentation. These results have implications for treatment of isolated small airway abnormalities that can be identified by non-invasive effort independent FOT particularly in symptomatic individuals with normal spirometry indices. This study underscores the need to study small airway function to understand physiologic changes over time following environmental and occupational lung injury.

Characterization of Persistent Uncontrolled Asthma Symptoms in Community Members Exposed to World Trade Center Dust and Fumes

“…We defined our study population to include those with normal spirometry values. We and others have previously reported the association of small airway dysfunction with symptoms and exposures in many WTC-exposed community members with preserved spirometry [ 16 , 35 , 43 , 44 , 67 ] and we therefore hypothesized that persistent respiratory symptoms would be associated with increased small airway dysfunction in this study. The median values for all measures of forced oscillation, including those considered to assess small airway function (R5–20), were slightly elevated (abnormal) in the group as a whole.…”

“…Controlled patients ( Table 3 ). We used a normal value of R 5 as < 3.96 cmH 2 O/L/s [ 33 , 34 , 35 ] and we considered a normal value of R 5–20 to be < 0.76 cmH 2 O/L/s based on previously published data [ 33 , 34 , 35 ]. There was a suggestion of an elevated median pre- and post-BD R 5–20 in Uncontrolled participants compared with Controlled, although this did not reach statistical significance.…”

“…Measurements included respiratory resistance at 5Hz (R 5 ) and the difference in resistance from 5 to 20Hz (R 5–20 ) as an index of frequency dependence of resistance (FDR), with higher values considered more abnormal. Upper limits of normal (ULN) for R 5 and R 5–20 (3.96 and 0.76 cmH 2 O/L/s, respectively) were based on previous reports of asymptomatic non-smoking subjects with normal spirometry [ 33 , 34 , 35 ]. A positive BD response for IOS measurements was defined as a decrease in R 5 of ≥1.40 cm H 2 O/L/s, based on the 95th percentile for BD response in healthy adults in normative data on forced oscillation [ 34 , 35 ].…”

Editorial for “Long-Term Health Effects of the 9/11 Disaster” in International Journal of Environmental Research and Public Health, 2019

“…An analysis of cleaning practices by residents in lower Manhattan showed that cleaning with dry methods was associated with more types of respiratory symptoms than other cleaning methods (Antao, 2019 [3]). Other papers delved into the underlying physical and biological aspects of pulmonary illness among persons exposed to 9/11 (Liu, 2019 [5]; Kwon, 2019 [6]; Pradhan, 2019 [7]). Liu et al (2019) used chest tomography (CT) and reported that firefighters with high intensity exposure on 9/11 had increased risk of bronchial wall thickening, emphysema, and air trapping.…”

“…They reported that given 9/11 exposure, having three or more MSBs increased airway hyperactivity beyond that associated with 9/11 exposure. Another paper that evaluated the bronchodilator response among community members exposed to 9/11 found that a proportion of small airway problems were irreversible, which was predicted by the bronchodilator response at initial visits (Pradhan, 2019 [7]). Two other papers evaluated the increased risk of asthma control issues and quality of life as a function of indoor allergens (Rojano, 2019 [8]) and air pollution/irritants (Yung, 2019 [9]).…”