key: cord-0808289-5x1c24tc
authors: Dang, Kelly T. L.; Garrido, Ameth N.; Prasad, Shivonne; Afanasyeva, Marina; Lipszyc, Joshua C.; Orchanian‐Cheff, Ani; Tarlo, Susan M.
title: The relationship between cleaning product exposure and respiratory and skin symptoms among healthcare workers in a hospital setting: A systematic review and meta‐analysis
date: 2022-04-22
journal: Health Sci Rep
DOI: 10.1002/hsr2.623
sha: 913f525856d9ccb064ce1d93452c5b301675f369
doc_id: 808289
cord_uid: 5x1c24tc

BACKGROUND AND AIMS: Several studies from multiple work settings have reported an increase in asthma and asthma‐like respiratory symptoms in workers exposed to cleaning or disinfecting agents. Hospital workers perform many cleaning and disinfecting activities and may be vulnerable to respiratory and skin symptoms caused by these agents. This systematic review and meta‐analysis aim to quantify the risk of asthma and asthma‐like symptoms in hospital workers exposed to cleaning/disinfecting agents. A secondary aim is to assess associated risks of skin symptoms in those studies. METHODS: MEDLINE, EMBASE, CDSR, CENTRAL, CINAHL databases, and references of relevant review articles were searched. NHLBI quality assessment tools were used to assess the quality of the included studies. A total of 2550 articles were retrieved and 34 studies met criteria to be included. The software R version 4.0.5 was used to perform the meta‐analysis. The random‐effects model was used to pool the results due to within‐studies heterogeneity. RESULTS: Meta‐analysis of 10 studies evaluating the association between occupational cleaning exposures and asthma demonstrated a 35% increased risk in exposed hospital workers (meta‐RR = 1.35, 95% CI: 1.09–1.68). The risk of asthma increased when workers were exposed to bleach compared with nonexposed workers (meta‐RR = 1.51, 95% CI: 0.54–4.18), but was not statistically significant. Two studies investigated the relationship between respiratory and skin symptoms and produced mixed results. CONCLUSIONS: The results suggest a need for preventive practices to reduce the risk of asthma and asthma‐like symptoms in hospital workers exposed to occupational cleaning/disinfecting agents. Trial registration number: CRD42020137804.

Cleaning and disinfecting tasks make up a significant portion of the duties of healthcare professionals and other workers in-hospital settings, especially to reduce risks of infection. These tasks can range from common housekeeping practices performed by cleaning staff, to surface and equipment cleaning and disinfection by healthcare workers such as nurses, respiratory therapists, physiotherapists, and radiographers. Multiple agents may be used for these tasks including quaternary ammonium compounds, bleach, and hydrogen peroxide.

Cleaning and disinfection of endoscopes and surgical equipment may include use of potential respiratory sensitizers such as enzymes, and aldehydes such as glutaraldehyde or ortho-phthaldehyde. Many of these tasks and agents have been associated with respiratory sensitization or irritation. 1, 2 Previous studies have reported an increased risk of asthma, asthma-like respiratory symptoms, as well as skin symptoms among healthcare workers exposed to cleaning or disinfecting agents. [3] [4] [5] Specifically, bleach has been associated with asthma-like respiratory symptoms and hand dermatitis 6 ; however, few studies have evaluated the relationship between respiratory and skin symptoms. Additionally, previous evidence of increased respiratory and skin symptoms among this population was derived from selfreported measures of exposures. Therefore, there is a potential for bias toward reporting cleaning agents with stronger odors, causing uncertainty regarding the specific agents that may cause both respiratory and skin symptoms among hospital workers. 7 A recent systematic review conducted by Romero Starke et al.

addressed a similar research question, the risk of obstructive respiratory diseases among healthcare workers exposed to cleaning or disinfecting agents compared with a nonexposed group 8 ; however, the review did not focus on all hospital workers and did not aim to evaluate skin symptoms among exposed healthcare workers with respiratory symptoms, nor to identify specific agents in the search strategy.

The aim of our study was to perform a comprehensive systematic review and meta-analysis of the available literature to quantify the risk of asthma and asthma-like symptoms in hospital workers exposed to cleaning or disinfecting agents. Furthermore, we aimed to identify risks of associated skin symptoms among the included studies, and the potential underlying causal agents. Embase (Ovid), and CINAHL (EBSCOhost). The search strategy consisted of using a combination of subject headings and free text terms for asthma, occupational exposures, healthcare personnel, and specific cleaning and disinfecting agents Terms for asthma included such terms as asthma, wheeze, bronchial hyperreactivity, respiratory hypersensitivity, and airflow obstruction among others. Terms for workplace exposure included such terms as occupational disease, occupational exposure, work, occupation, job-site, and occupational air pollutants among others. Terms for healthcare workers included varied types of healthcare personnel and health facilities among others, Terms for cleaning products included terms for disinfectants, detergents, surface-active agents, ammonium compounds, antiinfective agents, acetic acid, 2-propanol, chloramines, phenols, and decontamination procedures among others (full search strategies are included in the Table S1 ). The search strategy was adapted for each database. Additional studies were found by examining the references of relevant reviews. All studies that evaluated respiratory outcomes, symptoms, diseases, or lung function measures in relation to occupational cleaning or disinfecting tasks or products in any hospital workers were included. Among the included studies, data regarding skin outcomes were also sought. Inclusion criteria were grouped according to the population-exposure-comparator-outcome (PECO) framework:

• Population-populations in which individuals worked in a hospital setting;

• Exposures-studies of individuals with exposure at work to cleaning and/or disinfecting agents;

• Comparators-studies reporting comparative effect estimates, specifically case-control or cohort studies reporting risk, rate, or odds across groups exposed to different levels of cleaning and/or disinfecting agents (including binary comparisons of exposed/ unexposed), and across groups with and without asthma or asthma-like symptoms;

• Outcome-studies reporting incident asthma or asthma-like symptoms;

• Among subjects with asthma or asthma-like symptoms, the presence of reported skin symptoms was an additional outcome;

• English-language full-text available;

• Publication up to 6th August 2021.

We excluded studies that did not meet the inclusion criteria above. Randomized controlled trials, nonrandomized trials, cohort studies, and case control studies available in English were included. No restrictions regarding country, patient age, race, gender, and date were made. Case series, research in progress, conference proceedings, dissertations, books, editorials, letters, and review articles were excluded. Studies including occupational settings located outside of a medical centre or hospital were also excluded. A full list of inclusion and exclusion criteria is available in Table S2. 2.2 | Selection process, data collection process, and quality assessment Two reviewers independently screened the study titles and abstracts to exclude studies that did not meet the eligibility criteria. The full texts of the included studies were also screened independently by two reviewers. A consensus decision was made for disagreements regarding the inclusion of articles. If a disagreement was not resolved, a third reviewer was consulted for a final decision. Data extraction was completed independently by two reviewers using a modified form of the Cochrane Public Health Group Data Extraction and Assessment Template, adapted for this study according to the study aims and inclusion/exclusion criteria (Table S3) . Two reviewers independently assessed the risk of bias in the included studies using the NHLBI quality assessment tools, suitable for the type of study, for example, observational cohort and cross-sectional studies (Table S4) .

A third reviewer was consulted for a final, deciding rating when there were quality assessment differences. The final scoring classification was ranked as poor, fair, or good.

Meta-analyses were considered to quantify the risk of respiratory and skin symptoms that are associated with cleaning and disinfecting agents.

Studies included in the systematic review that received a "fair" or "good" quality score according to the NHLBI quality assessment tools were considered for the meta-analyses. The main reported effect measures between occupational exposure to cleaning or disinfecting products and asthma or asthma-like symptoms were pooled using the random-effects model. The random-effects model was chosen in consideration of the heterogeneity within the studies in terms of populations, age, and exposures. The Mantel-Haenszel method was used to calculate the weights of the studies. Higgins I 2 statistic was used to determine withinstudies heterogeneity. A threshold of I 2 ≥ 50% was used to determine substantial within-studies heterogeneity. 9 Subgroup analysis by study design was performed. Pooled risk ratio estimates were presented as meta-relative risks (RRs) and 95% CIs. Statistical significance was determined by a p-value of less than 0.05. The package "meta" in the software R version 4.0.5 was used to perform the meta-analysis. 10 Funnel plots and Egger's test results were used to assess potential publication bias. Subgroup analyses were performed post-hoc to determine associations with different study classifications of asthma and asthma-like symptoms, and with specific reported exposures when comparable studies were available for meta-analyses.

A total of 2549 articles were retrieved from all databases, with one additional article identified through manual searching. There were 158 duplicate articles removed and 2315 articles excluded from title and abstract screening. The full texts of 77 articles were screened. A total of 34 articles met the study inclusion criteria. Reasons for the exclusion of studies are listed in the PRISMA flow diagram (Figure 1 ).

Based on risk of bias assessments, most of the included studies received a "fair" quality score. Notably, one study received "poor" quality scores, 4 and four studies received "good" quality scores. [11] [12] [13] [14] One study received a "good/fair" quality assessment score because it met 10 of 14 criteria, however, the participation rate and sample size was low, resulting in a "good/fair" quality assessment rating. 15 Overall, the quality of the studies was fair. There were no randomized controlled studies and most studies were cross-sectional. A quantitative meta-analysis was performed among ten "fair" or "good" quality studies evaluating the association between exposure to cleaning or disinfecting tasks or agents and asthma risk. A quantitative metaanalysis was also performed among three "fair" or "good" quality studies that evaluated the association between bleach exposure and asthma risk. Results of other studies could not be pooled due to important differences in how the exposures and outcomes were defined, or differences in the comparison groups used.

Of the 34 studies meeting inclusion criteria, 23 studies investigated associations between occupational cleaning exposures and asthma.

Tables 1 and 2 include the tasks and exposures reported in these studies. Only studies that investigated asthma as an outcome were included in this portion of the systematic review and Table 1 . Twelve studies that investigated only asthma-like symptoms were summarized separately in Table 2 . When studies investigated multiple outcomes, such as asthma, asthma-like symptoms, and skin symptoms, then they were included in each of the respective tables (Tables 1-3) .

Five of the 23 studies were prospective and the remainder were cross-sectional or retrospective in design. Thirteen studies were performed in the United States of America, 12, 13, 15, 16, [18] [19] [20] 23, 26, 27, [29] [30] [31] and one study was performed in the United Kingdom 24 among healthcare and other hospital workers. Three studies were performed in Canada, 5, 17, 21 two studies were performed in France, 1,25 one study was performed in Sweden, 22 and one study collected data from participants located in ten European countries. 11 One study was performed in Australia 28 and one study was performed in the United States of America and Canada. 14 Occupational exposures to cleaning or disinfecting tasks or agents were assessed by self-report with the exception of five studies. Four studies used a job-exposure matrix (JEM) or a job task exposure matrix (JTEM) to estimate occupational exposure to cleaning agents 12, 13, 19, 20 and one study used three methods to estimate exposure to cleaning agents: self-report, expert assessment, and an asthma-specific JEM. 1 With regard to outcome definitions for asthma, six studies used current asthma, described as presently having asthma. 1, 16, 23, [26] [27] [28] Twelve studies used the definition of new-onset asthma, reported asthma, or post-hire asthma, that were defined as asthma onset diagnosed after entry into a healthcare profession. 5 adult-onset asthma, defined as asthma reported at 16 years of age or older. 22 Two studies investigated asthma incidence in prospective cohort studies of female registered nurses. 14, 30 Last, one study assessed asthma control using the Asthma Control Test. 13 All studies received a risk bias assessment score of "fair" or "good."

Exposure to cleaning and disinfecting tasks or cleaning and disinfecting products was associated with increased asthma risk in most studies. 1, 5, 11, 12, 14, 17, 19, 20, 22, 23, 25, 27, 29, 31 Of note, two studies conducted different analyses using the same data set. 29, 31 An increase in the frequency of performed disinfection tasks from never or monthly to weekly or daily was associated with increased odds of new-onset asthma (odds ratio [OR] = 3.13, 95% CI: 1.05-9.35). 25 The use of disinfectants to clean medical instruments was associated with poorly controlled asthma (OR = 1.37, 95% CI: 1.05-1.79) and very poorly controlled asthma (OR = 1.88, 95% CI: 1.38-2.56). 13 Among asthmatic hospital workers, the most frequently reported exposure agents were glutaraldehyde (38%), latex (26%), and various cleaning products (15%). 24 Latex is not a cleaning product; however, it may be used during cleaning tasks and can be a confounding factor when assessing the effects of cleaning and disinfecting agents on asthma risk. When considered separately, exposure to latex was associated with an increased risk of new-onset asthma and current asthma. 11, 20 Three studies reported that exposure to bleach significantly increased the risk of current, new-onset, or undiagnosed asthma among hospital workers. 1, 11, 31 Similarly, one study also found that both latex and bleach exposures were associated with increased odds of new-onset asthma; however, these results were not statistically significant. 25 Exposure to quaternary ammonium compounds was found to result in an increased risk of new-onset asthma among hospital workers. 1, 25 One study found that exposure to formaldehyde, glutaraldehyde, hypochlorite bleach, hydrogen peroxide, and enzymatic cleaners was associated with poor asthma control (p < 0.05 for all exposures), but exposure to alcohol and quaternary ammonium compounds was not associated with poor asthma control. 13 Several studies investigated glutaraldehyde as an occupational cleaning exposure. Dimich-Ward et al. found that hospital healthcare workers exposed to glutaraldehyde had an increased risk of newonset asthma compared to unexposed healthcare workers. 17 F I G U R E 1 PRISMA flow diagram illustrating the process of screening and selecting articles related to occupational cleaning exposures and respiratory symptoms from a search of electronic bibliographic databases.

T A B L E 1 Summary of epidemiological studies (chronological order) assessing the associations between cleaning tasks or agents and asthma risks reported in these studies were not statistically significant. 16, 25 Two studies found contrasting results. Casey et al. evaluated the association between a surface disinfectant product containing hydrogen peroxide, peracetic acid, and acetic acid. No significant differences between current asthma diagnoses were found among product users and nonusers (p = 0.66). 26 Last, Dumas et al. found no significant association between weekly use of disinfectants and incident asthma, and no significant association between high-level exposure to specific disinfectants and incident asthma. 30 

Ten studies evaluating asthma with fair or good quality scores were selected for a meta-analysis. 1, 5, 6, 11, 16, 17, 22, 25, 26, 29 When studies presented multiple risk estimates for asthma, the quantitative summary that defined occupational asthma the best was selected.

For instance, quantitative summaries for new-onset asthma were selected over quantitative summaries for ever asthma diagnoses. The outcome definitions for the studies included in the meta-analysis included current asthma (ever asthma and report of asthma attacks, respiratory symptoms, or treatment of asthma in the past 12 months, or physician-diagnosed asthma that was still present), 1, 6, 16, 26 new-onset asthma, reported asthma, or post-hire asthma (reported onset of physician-diagnosed asthma after entering a healthcare profession), 5, 11, 17, 25, 29 and adult-onset asthma (asthma reported at the age of 16 years old or later). 22 The pooled meta-analysis of the 10 studies demonstrated a significant 35% increased risk for asthma among hospital healthcare workers exposed to cleaning or disinfecting tasks or agents (meta-RR = 1.35, 95% CI: 1.09-1.68, p = 0.01, I 2 = 30%) (Figure 2 ). The pooled risk estimate was higher among cross-sectional studies (meta-RR = 1.45; 95% CI: 1.10-1.90, p = 0.01, I 2 = 25%) (Figure 2 ). No evidence of publication bias was observed (Egger's test p = 0.66) ( Figure S1 ).

Before 2000, powdered latex gloves were used as personal protective equipment by most hospital staff, including cleaners. 12 After 2000, there was a reduction in usage of powdered latex gloves due to increasing reports of latex allergy reactions. 12 Therefore, latex may have been a confounding factor in estimating the risk from cleaning agents. A meta-analysis on studies conducted after 2000 was performed to identify any change in risks over time that may have been associated with decreased use of powdered latex gloves or other preventive exposure measures in hospitals since that time.

The risk of asthma attributed to cleaning or disinfecting tasks or agents decreased from a 35% increased risk to a 28% increased risk after 2000 (meta-RR = 1.28, 95% CI: 1.04-1.57, p = 0.03, I 2 = 14%)

F I G U R E 2 Forest plot illustrating a meta-analysis of 10 studies evaluating the association between exposure to cleaning or disinfecting tasks or agents and asthma risk; RR, relative risk. Among cross-sectional studies, an additional subgroup analysis by study definition of asthma was performed. The results of five of the eight cross-sectional studies that evaluated new-onset asthma, reported asthma, or adult-onset asthma were pooled, 5, 17, 22, 25, 29 excluding studies that evaluated current asthma. 6, 16, 26 An additional subgroup analysis was performed to focus on new-onset asthma, adult-onset asthma, posthire asthma and post-hire reported asthma, since asthma caused by occupational cleaning exposures is more expected to occur within these subgroups. When focusing on new-onset asthma, adult-onset asthma, post-hire asthma, or reported asthma outcomes, a nonsignificant 46% increased risk was determined among healthcare workers exposed to cleaning or disinfecting agents or tasks (meta-RR = 1.46, 95% CI: 0.99-2.14, p > 0.05, I 2 = 20%) ( Figure 4 ).

No evidence of publication bias was observed (Egger's test p = 0.52) ( Figure S3 ).

The pooled meta-analysis of three studies evaluating asthma in relation to bleach exposure demonstrated a nonsignificant 51%

increased risk among exposed healthcare workers (meta-RR = 1.51, 95% CI: 0.54-4.18, p = 0.23; I 2 = 48%) ( Figure 5 ). 1, 11, 25 No evidence of publication bias was observed (Egger's test Figure S4 ).

Twenty-two studies assessed the associations between cleaning tasks or agents and lower and upper respiratory tract symptoms (LRTS and URTS respectively) ( Table 2 ). All but one of the studies used a cross-sectional study design. All studies received a quality assessment score of "fair" or "good: except for 1 study, which received a "poor" quality score. 4 Nineteen of the 21 "fair" or "good" quality studies evaluated only LRTS or asthma-like symptoms, such as wheeze, cough, shortness of breath, and breathlessness. [3] [4] [5] [6] 12, 15, 17, 19, 22, [26] [27] [28] [29] 32, [35] [36] [37] [38] [39] Most reported increased risks of LTRS associated with cleaning tasks and disinfectants. 3, 5, 6, 17, 22, 26, 27, 29, [35] [36] [37] [38] One study reported that the odds of workrelated asthma symptoms such as shortness of breath and wheeze increased in a dose-dependent manner (OR = 2.64, 95% CI: 0.57-12.14 for once a week exposure to OR = 5.37, 95% CI: 1.43-20.16 for more than once daily exposure). 35 One study found a nearly 10-fold risk of reactive airways dysfunction syndrome (RADS) in hospital workers exposed to 100% acetic acid (OR = 9.8, 95% CI: 0.902-264.6). 32 Four studies reported increased odds of bronchial hyperresponsiveness (BHR)related symptoms, such as trouble breathing, wheezing, shortness of breath, and chest tightness, associated with general cleaning tasks and cleaning and disinfectant products. 12, 15, 19, 29 In particular, Patel et al. Four studies evaluated URTS in addition to LRTS. 33, 34, 38, 40 One study demonstrated a significant increase in worsening nose and F I G U R E 3 Forest plot illustrating a metaanalysis of nine studies conducted after the year 2000 evaluating the association between exposure to cleaning or disinfecting tasks or agents and asthma risk; RR, relative risk.

F I G U R E 4 Forest plot illustrating a metaanalysis of five cross-sectional studies evaluating the association between exposure to cleaning or disinfecting tasks or agents and risk of newonset, adult-onset, post-hire, and reported asthma; RR, relative risk.

throat problems among nurses exposed to glutaraldehyde (p < 0.002). 16 Similarly, a second study showed a significant increase in nose (p < 0.01) and eye irritation (p < 0.05) in nurses exposed to glutaraldehyde. 33 Rankooy et al. found that the prevalence of nasal irritation was significantly higher in a group exposed to formaldehyde compared with a control group (p < 0.05). 38 Last, Nayebzadeh et al.

reported an increased prevalence of LRTS and URTS when unsafe work practices were occurring. 34 Examples of unsafe work practices included leaving unused containers uncovered, the inappropriate storing or disposing contaminated linen and paper towels, and causing spills or leakages of solution from containers. 34 

The pooled meta-analysis of four studies evaluating the risk of wheeze among healthcare workers exposed to cleaning or disinfecting tasks or agents demonstrated a nonsignificant 55% increased risk among exposed healthcare workers (meta-RR = 1.55, 95% CI: 0.85-2.82, p = 0.10; I 2 = 49%) ( Figure 6 ). 5, 17, 26, 29 No evidence of publication bias was observed (Egger's test p = 0.80) ( Figure S5 ).

Only two studies directly investigated the risk of skin symptoms in relation to respiratory symptoms. 4,28 Lipińska-Ojrzanowska et al.

found that healthcentre cleaners with respiratory symptoms had significantly increased odds of having skin symptoms compared with healthcentre cleaners without respiratory symptoms (OR = 2.62, 95% CI: 1.11-6.21); however, this study received a poor quality assessment score, indicating a high risk of bias. 4 Barnes et al. found that 40.1% of exposed healthcare workers with hay fever or asthma reported localized rash, 79.5% reported dry skin, and 36.6% reported eczema in response to chlorhexidine. 28 No significant association was found between the respiratory symptoms and skin symptoms experienced among exposed healthcare workers with eczema or contact dermatitis. 28 

This systematic review and meta-analysis found a 35% increased asthma risk among healthcare and other hospital workers exposed to cleaning and disinfecting tasks or cleaning and disinfecting agents, compared with other workers (p = 0.01). After 2000 the excess risk of asthma attributed to cleaning or disinfecting tasks or agents decreased to 28%, suggesting a possible earlier confounding effect of natural rubber latex exposure and/or other exposure changes. The risk of asthma attributed to cleaning and disinfecting tasks or agents increased (to 45%) when subgroup analysis was performed to focus on new-onset asthma and adult-onset asthma diagnoses; however, this increased risk was not statistically significant. Assessment of specific agents showed a nonsignificant 51% increased asthma risk associated with bleach exposure, and most studies also reported an increased asthma risk associated with exposure to glutaraldehyde, bleach, and quaternary ammonium compounds. No exposureresponse relationships between potential causal agents and reported asthma could be determined due to the lack of quantitative exposure analysis. Four studies reported no statistically significant differences between current asthma diagnoses among disinfectant product users F I G U R E 5 Forest plot illustrating a metaanalysis of three studies evaluating the association between bleach exposure and asthma risk; RR, relative risk.

F I G U R E 6 Forest plot illustrating a metaanalysis of four studies evaluating the association between exposure to cleaning or disinfecting tasks or agents and risk of wheeze; RR, relative risk. and nonusers. 16, 25, 26, 30 These contrasting results may be due to the possibility that workers without direct use of disinfectants were exposed to the vapors of the disinfectant products, which can also induce asthma. 26 Also, the study population of one of the studies that found contrasting results was restricted to nurses who had no asthma after over 20 years of occupational exposure. 30 The authors then investigated the development of asthma among these nurses in the following 6 years, and found incident asthma to be unrelated to disinfectants. 30 Therefore, the unique characteristics of this limited study population and a "healthy worker" effect may have contributed to the unexpected results found.

Cleaning and disinfecting tasks or agents were also found to be associated with an increased risk of LRTS and URTS in studies that investigated asthma-like symptoms and URTS, such as nasal irritation.

The meta-analysis for wheezing symptoms found a nonsignificant 55% increased risk among exposed healthcare workers.

Among the studies included in the systematic review, there were very limited results regarding the relationship between respiratory and skin symptoms. One study evaluated the relationship between respiratory and skin symptoms and found increased odds of skin symptoms in healthcare workers with respiratory symptoms 4 ;

however, this study was given a "poor" quality assessment score, with a high risk of bias potentially affecting the reliability of the results. A second study found that exposed healthcare workers with hay fever or asthma also reported skin symptoms such as localized rash, dry skin, and eczema in response to chlorhexidine, suggesting a potential relationship between respiratory and skin symptoms; however, no significant association was found between the respiratory symptoms and skin symptoms experienced among exposed healthcare workers with eczema or contact dermatitis. 28 Lee et al.

reported that contact dermatitis was significantly more frequent in workers with chemical-related symptoms compared with workers without chemical-related symptoms 3 ; however, the outcome definition for chemical-related symptoms in this study included symptoms associated with respiratory, skin, gastrointestinal, eye, or nervous systems, making it difficult to discern the relationship between respiratory symptoms and contact dermatitis specifically. Due to the limited available data, no conclusions can be drawn about possible associations between respiratory and skin symptoms related to cleaning and disinfecting agents in hospital workers.

A strength of this systematic review was its comprehensiveness, as indicated by a lack of observed publication bias. Also, the systematic review included independent assessment from a minimum of two reviewers for the title and abstract screening, full-text screening, and risk of bias assessment stages of the methods. Another strength is that most of the included studies have a low risk of bias assessment, as deemed by a "fair" or "good" quality assessment score. Only one study received a "poor" quality assessment score, and the risk of bias in this study was considered in the interpretation of the results. Last, pooled risk estimates were obtained that quantify the risk of asthma among healthcare workers exposed to cleaning or disinfecting agents or tasks.

The pooled risk estimates can be used to inform future public health interventions and research studies regarding similar topics.

One of the limitations of this systematic review is the exclusion of articles written in languages other than English. Additionally, almost all of the included studies used self-report measures to collect data, which is subject to recall bias. For instance, cleaning products and disinfectants that have a more pungent and noxious smell might be more memorable. 7 In a study conducted in Arizona, participants with asthma were more likely to report feeling sick in the presence of compounds with a strong odor, such as cleaning agents. 7 population. An association between asthma history and subsequent job changes in nurses was previously found, supporting the possibility of the healthy worker effect bias in cross-sectional studies regarding disinfectant exposures. 42 More prospective cohort studies that follow healthcare workers from early stages of their career and examine the influence of exposure duration, similar to the study conducted by Dumas et al., would limit the healthy worker bias effect. 14 

In conclusion, this review found a higher risk of asthma among healthcare workers exposed to cleaning or disinfecting tasks or agents. These findings are consistent with the results of previously conducted systematic reviews. 8, 43 Compared with this review, both previous reviews determined a greater increase in asthma risk associated with cleaning or disinfecting tasks. 8, 43 The limitations found in this review may contribute to a potential underestimation of the risk. The findings highlight the importance of implementing safe work practices and control measures that protect healthcare workers from potentially harmful occupational cleaning and disinfecting exposures. The results of this review are especially relevant during the COVID-19 pandemic, when the use of cleaning and disinfecting agents has increased to prevent the transmission of the virus. Future studies using a prospective cohort design and quantitative exposure assessments of specific cleaning or disinfecting agents are recommended because they will decrease the potential of healthy worker effect bias and allow for the determination of an exposure-response relationship. Measuring exposure to specific cleaning or disinfecting agents in future studies will also help to further elucidate underlying causal agents. Also, further research regarding skin symptoms among healthcare workers with asthma-like respiratory symptoms is suggested. The studies that were included in this review evaluated asthma-like respiratory symptoms but have not fully explored the skin symptoms that may be concurrently occurring among healthcare workers with respiratory symptoms. Preventive measures that have been advised for those working with cleaning/disinfecting agents have included use of safe products when possible, safety education of workers, appropriate use of protective equipment, and good ventilation. 44 Filling these gaps in knowledge could help with earlier prevention and treatment interventions to take place for these workers. 

The authors declare no conflicts of interest.

Additional data are available in the online supplement.

The lead author (manuscript guarantor) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted;

and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Ani Orchanian-Cheff http://orcid.org/0000-0002-9943-2692

Susan M. Tarlo http://orcid.org/0000-0002-4746-5310

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