J Korean Med Sci.  2022 Nov;37(44):e319. 10.3346/jkms.2022.37.e319.

Reduced Diffusing Capacity in Humidifier Disinfectant-Associated Asthma Versus Typical Asthma: A Retrospective Case Control Study

Affiliations
  • 1Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
  • 2Divisions of Preventive, Occupational & Aerospace Medicine and Pulmonary & Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
  • 3Department of Occupational and Environmental Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

Abstract

Background
Humidifier disinfectant-related lung injury (HDLI) is a severe form of toxic inhalational pulmonary parenchymal damage found in residents of South Korea previously exposed to specific guanidine-based compounds present in humidifier disinfectants (HD). HD-associated asthma (HDA), which is similar to irritant-induced asthma, has been recognized in victims with asthma-like symptoms and is probably caused by airway injury. In this study, diffusing capacity of the lung for carbon monoxide (DL CO ) in individuals with HDA was compared to that in individuals with pre-existing asthma without HD exposure.
Methods
We retrospectively compared data, including DLCO values, of 70 patients with HDA with that of 79 patients having pre-existing asthma without any known exposure to HD (controls). Multiple linear regression analysis and logistic regression analysis were performed to confirm the association between HD exposure and DL CO after controlling for confounding factors. The correlation between DLCO and several indicators related to HD exposure was evaluated in patients with HDA. Result: The mean DLCO was significantly lower in the HDA group than in the control group (81.9% vs. 88.6%; P = 0.021). The mean DLCO of asthma patients with definite HD exposure was significantly lower than that of asthma patients with lesser exposure (P for trend = 0.002). In multivariable regression models, DLCO in the HDA group decreased by 5.8%, and patients with HDA were 2.1-fold more likely to have a lower DLCO than the controls. Pathway analysis showed that exposure to HD directly affected DLCO values and indirectly affected its measurement through a decrease in the forced vital capacity (FVC). Correlation analysis indicated a significant inverse correlation between DLCO % and cumulative HD exposure time.
Conclusion
DLCO was lower in patients with HDA than in asthma patients without HD exposure, and decreased FVC partially mediated this effect. Therefore, monitoring the DL CO may be useful for early diagnosis of HDA in patients with asthma symptoms and history of HD exposure.

Keyword

Humidifier Disinfectant; Lung; Diffusing Capacity; Exposure

Figure

  • Fig. 1 Flow chart for the selection of study subjects. (A) Selection of patients with humidifier disinfectant-associated asthma. (B) Selection of asthma patients without exposure to humidifier disinfectant.HDA = humidifier disinfectant-associated asthma, DLCO = diffusing capacity of the lung for carbon monoxide, ILD = interstitial lung disease, AHR = airway hyperresponsiveness, HD = humidifier disinfectant, COPD = chronic obstructive pulmonary disease.aCOPD (n = 11), partial resections of the lung (n = 4), advanced lung cancer (n = 1), advanced esophageal cancer (n = 2), lung metastasis (n = 2), history of radiation treatment for breast cancer (n = 1), suspected acute pneumonia (n = 6), pulmonary tuberculosis sequelae (n = 2), cystic fibrosis (n = 1), pleural adhesion (n = 3), pulmonary edema or pleural effusion (n = 2), pneumothorax (n = 1), severe bronchiectasis (n = 3), and Churg-Strauss syndrome (n = 3).

  • Fig. 2 Comparison of the diffusing capacity between the HDA and asthma without HD exposure groups.Plots indicate individual data points and mean ± standard error of DLCO% predicted (horizontal line and vertical bar). P value for Student’s t-test (P = 0.021).DLCO = diffusing capacity of the lung for carbon monoxide, HDA = humidifier disinfectant-associated asthma, HD = humidifier disinfectant.

  • Fig. 3 Diffusing capacity of asthma patients with definite, non-definite, and no exposure to HD.Plots indicate individual data points and mean ± standard error of DLCO% predicted (horizontal line and vertical bar). The P value for the trend was analyzed by Jonckheere-Terpstra test (P = 0.002). There was a statistical difference in the mean DLCO% of asthma patients with definite exposure (n = 23) and those with non-definite exposure group (probable + possible + indeterminate exposure, n = 47) (71.8 ± 21.9% vs. 86.9 ± 19.7%; P = 0.008 by Student’s t-test).DLCO = diffusing capacity of the lung for carbon monoxide, HD = humidifier disinfectant.

  • Fig. 4 Regression pathway analyses.The proportion of the mediated effect is obtained by dividing the indirect effect by the total effect. Thus, the mediation proportion {(−7.091*0.444)/−5.831} is calculated to be 54% of the variance, showing that FVC was a significant partial mediator of the relationship between exposure and DLCO. The P values shown are for a one-tailed probability, after adjusting for body mass index.DLCO = diffusing capacity of the lung for carbon monoxide, FVC = forced vital capacity.

  • Fig. 5 Correlation between cumulative usage time and DLCO.Cumulative usage time (hours) was changed to a log10 scale. The negative slope line indicates the correlation as analyzed by the Spearman rank test.DLCO = diffusing capacity of the lung for carbon monoxide.


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