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

• Pak C
• Cowl CT
• Kim JH
• Kang BJ
• Lee T
• Jegal Y
• Ra SW
• Kim Y

• KMID: 2535182
• DOI: http://doi.org/10.3346/jkms.2022.37.e319

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 DL_CO 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 DL_CO and several indicators related to HD exposure was evaluated in patients with HDA. Result: The mean DL_CO was significantly lower in the HDA group than in the control group (81.9% vs. 88.6%; P = 0.021). The mean DL_CO 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, DL_CO in the HDA group decreased by 5.8%, and patients with HDA were 2.1-fold more likely to have a lower DL_CO than the controls. Pathway analysis showed that exposure to HD directly affected DL_CO values and indirectly affected its measurement through a decrease in the forced vital capacity (FVC). Correlation analysis indicated a significant inverse correlation between DL_CO % and cumulative HD exposure time.
Conclusion
DL_CO 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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