Workplace interventions for preventing work-related

Workplace interventions for preventing work-related rhinitis and rhinosinusitis (Protocol) Bakon SK, Muhamad NA, Mohamad ZA, Adon MY, Arip M, Airaksinen L, Faizal Bakhtiar M, Hailani I, Murad S, Kamaluddin MA, Hannu TJ

This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 7 http://www.thecochranelibrary.com

Workplace interventions for preventing work-related rhinitis and rhinosinusitis (Protocol) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . ABSTRACT . . . . . . . . . BACKGROUND . . . . . . . OBJECTIVES . . . . . . . . METHODS . . . . . . . . . ACKNOWLEDGEMENTS . . . REFERENCES . . . . . . . . APPENDICES . . . . . . . . CONTRIBUTIONS OF AUTHORS DECLARATIONS OF INTEREST .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .


. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . .

1 1 1 3 3 7 7 10 11 11

i

[Intervention Protocol]

Workplace interventions for preventing work-related rhinitis and rhinosinusitis Sophia K Bakon1 , Nor Asiah Muhamad2 , Zuraifah Asrah Mohamad1 , Mohd Yusoff Adon1 , Masita Arip3 , Liisa Airaksinen4 , Mohamed Faizal Bakhtiar5 , Iskandar Hailani6 , Shahnaz Murad7 , Muhammad A Kamaluddin1 , Timo J Hannu8 ,9 1 Environmental Health Research Centre, Institute

for Medical Research, Kuala Lumpur, Malaysia. 2 Medical Research Resource Centre, Institute for Medical Research, Kuala Lumpur, Malaysia. 3 Allergy and Immunology Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia. 4 Occupational Medicine, Finnish Institute of Occupational Health, Helsinki, Finland. 5 Allergy and Immunology Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia. 6 Otorhinolaryngology, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia. 7 Office of The Director General of Health, Ministry of Health, Kuala Lumpur, Malaysia. 8 Department of Public Health, University of Helsinki, Helsinki, Finland. 9 Department of Clinical Medicine, Unit of Occupational Health, University of Turku, Turku, Finland Contact address: Nor Asiah Muhamad, Medical Research Resource Centre, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, 50588, Malaysia. [email protected]. Editorial group: Cochrane Work Group. Publication status and date: New, published in Issue 7, 2015. Citation: Bakon SK, Muhamad NA, Mohamad ZA, Adon MY, Arip M, Airaksinen L, Faizal Bakhtiar M, Hailani I, Murad S, Kamaluddin MA, Hannu TJ. Workplace interventions for preventing work-related rhinitis and rhinosinusitis. Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.: CD011816. DOI: 10.1002/14651858.CD011816. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of interventions aimed at preventing the onset of WRR and WRRS in occupational settings. We will combine findings of rhinitis and rhinosinusitis in this review due to their similarity in definition, presentation and reported effects, but we will separate the two entities if possible in our subgroup analysis.

BACKGROUND

Description of the condition Work-related rhinitis and rhinosinusitis are major problems for workers worldwide. Rhinitis is defined by the British Society for Allergy and Clinical Immunology as an inflammatory condition of the nose, which is characterised by intermittent or persistent symptoms consisting of nasal congestion, sneezing, rhinorrhoea and itching (Scadding 2008; Zhao 2012). Work-related rhinitis

(WRR), also known as occupational rhinitis, is caused by conditions attributable to a work-specific environment rather than stimuli encountered outside the workplace; it can be categorised into onset WRR or an exacerbation of pre-existing rhinitis due to workplace exposures (Moscato 2009). For its part, rhinosinusitis is defined as an inflammatory condition of the nose and paranasal sinuses characterised by nasal blockage, obstruction, congestion or discharge. It may be accompanied by facial discomfort or reduced sense of smell, supported by endoscopic signs of nasal polyps, mucopurulent discharge or mucosal oedema, primarily from the mid-


1

dle meatus. Mucosal changes within the osteomeatal complex and sinuses may also be apparent in a CT scan (Fokkens 2012). Rhinitis and rhinosinusitis are part of the same aetiological spectrum, and their occupational forms, WRR and work-related rhinosinusitis (WRRS), cause increased sickness absence, loss of productivity and increased medical expenses. Work productivity losses attributable to allergic rhinitis in the USA in 1995 were estimated to be between USD 2.4 billion and USD 4.6 billion (Crystal-Peters 2000). As WRR and WRRS involve both allergic and non-allergic components, and not all allergic rhinitis is due to WRR or WRRS, those estimates are of limited usefulness in estimating the cost of WRR and WRRS. Estimates for the overall cost burden of WRR and WRRS have not been reported. Although the prevalence of WRR and WRRS varies from 2% to 87% across settings, depending on the presence of different workplace risk factors, it is consistently reported to be more common than occupational asthma, another well-known illness on the same spectrum (Moscato 2009; Siracusa 2000). Certain occupations are reported to have increased risk of WRR, including furriers, bakers, livestock breeders, food-processing workers, veterinarians, farmers, electronic or electrical products assemblers, boat builders and workers in the detergent industry (Elliott 2005; Gautrin 2001; Hytonen 1997; Sarlo 2003; Zhao 2012). There are several aetiological categories of rhinitis and rhinosinusitis (Slavin 2010). • Irritational: non-specific inflammation of the nose that has no immunologic or allergic basis. Exposure to substances such as cigarette smoke, formalin and capsaicin results in the release of substance P, a sensory transmitter that triggers a neurogenic inflammatory response. This type of WRR is seen in people who work in an enclosed environment and who are exposed to materials such as paints, talcum and coal dust. • Corrosive: the result of exposure to a high concentration of irritating and soluble chemical gases, causing sufficient nasal inflammation that the mucosa may break down and ulcerate, similar to a chemical burn. Common causes include exposure to substances with high water solubility and chemical reactivity, such as chlorine, sulphur dioxide, ammonia and formaldehyde. Corrosive WRR can lead to permanent changes in physiological functions of the nose, such as loss of smell. • Immunologic: allergic response that may or may not be IgE-mediated, with resultant early and late nasal and sinus reactions, respectively. • Annoyance: incident in individuals with a heightened olfactory awareness to substances such as perfumes and detergents. The likelihood of developing annoyance reactions is increased by nasal polyposis, sinusitis, smoking and overuse of over-the-counter nasal decongestants or illicit drugs. However, the category of annoyance is not included consistently in all definitions (Moscato 2009), as other causes such as psychosocial factors are considered likely to contribute to this reaction. Certain high-molecular weight particles have a tendency to elicit

an allergic response (Ameille 2013). An example of this is psyllium, a major component of popular bulk-forming laxatives affecting people who work in laxative-producing factories or nurses who dispense the medication. Similarly, guar gum is commonly reported as a cause of WRR in the food and carpet industries. Carpet workers may become sensitive to guar gum through its use as a fixator for dye and fibre as well as an insulator in rubber cables.

Description of the intervention Because WRR and WRRS are part of a spectrum, they are likely to respond similarly to interventions. Primary prevention involves eliminating or controlling exposure to sensitising agents in order to prevent individuals from developing the condition, while secondary prevention applies many of the same interventions as a way to control or treat people who have already acquired WRR or WRRS. While elimination of the sensitising agent is the ideal intervention, reducing occupational exposure, for example through the use of personal protective equipment like respirators, should be considered if this is not an option. The Hazard Identification Risk Assessment and Risk Control (HIRARC) framework is commonly used as a basis for occupational health and safety measures, and it generally prioritises risk control options in the following orders; elimination of the agent or compound; substitution with a less sensitising agent; engineering controls;administrative controls; training and education; and personal protective equipment. Curti 2012 have applied a very similar formula to classify measures to control occupational asthma, whose aetiology overlaps considerably with WRR and WRRS as a disease entity. Thus, this classification constitutes a good basis for our Cochrane review.

How the intervention might work Eliminating workplace exposure to sensitising agents or substituting these agents with non-sensitising agents theoretically would be the most effective approaches to minimising the incidence of workrelated rhinitis, and it is known to prevent WRR and WRRS and work-related asthma (Wright 2014). However, total elimination is usually hard to achieve because changing industrial production relies on technological changes. Curti 2012 were able to provide a few appropriate examples, including the removal of some chemical compounds from radiology units when digital imaging came into use (Liss 2003) and the substitution of glutaraldehyde with other chemicals less likely to sensitise in the sterilisation process of medical instruments (Fujita 2006). If elimination or substitution are not feasible, engineering controls including process enclosure, ventilation, process or equipment modification can also reduce exposure. One good example is the encapsulation of enzymes in detergent production (Schweigert 2000).


2

Administrative controls, such as job rotation or adoption of rest periods, can limit the number of exposed workers or their duration of exposure. At the same time, manager and staff training and education in workplace safety practices and in the selection and proper use of respiratory protective devices (Dressel 2007; HSE 2013), can increase compliance with protective measures (Sakunkoo 2012) and reduce WRR and WRRS. Logically, training should also be accompanied by the provision of personal protective equipment to reduce workers’ exposure to sensitising agents (Sakunkoo 2012). Primary prevention of WRR or WRRS might also be achieved by excluding people with a high possibility of sensitisation from highrisk jobs. For example, a Cochrane review on pre-employment examinations found that the inclusion of a bronchial challenge reduced occupational asthma (Mahmud 2010).

Why it is important to do this review Rhinitis is a difficult condition to treat. In published Cochrane reviews on various medical interventions that mainly target the individuals in treating allergic rhinitis and related illnesses, some show a benefit (Calderon 2007; Radulovic 2010; Taramarcaz 2003), while others are inconclusive (Cheng 2006; Harvey 2007; Mishra 2012; Nasser 2010; Nurmatov 2012; Sacks 2011). There are several relevant non-Cochrane reviews published over the last 12 years that cover part of our topic. Balkissoon 2002 and Chan 2009 provide a general overview of work-related rhinitis, including diagnosis and management strategies. However, the papers did not evaluate a specific intervention or a type of management strategy adapted to the workplace. There was also a lack of sufficient clarity on the crucial steps in a systematic review. Hellgren 2008 is also an overview paper, but it focuses on “new insights on occupational rhinosinusitis, including the impact on health-related quality of life”. Zacharek 2004 gives an overview on the pathophysiology of persistent rhinosinusitis at the molecular level. Marple 2009 provides a relatively recent and comprehensive overview of chronic rhinosinusitis, including work-related rhinosinusitis. However, there was no specific intervention evaluated in accordance to the steps required in a systematic review. In recent years, two very similar reviews on occupational rhinitis have been published by the European Academy of Allergy and Clinical Immunology (EAACI) (EAACI 2008; Moscato 2009). Their key message relates to primary prevention of occupational rhinitis by focusing on reducing exposure to potentially sensitising agents. As examples of effective prevention resulting from reduction of exposure, the reviews mention strategies used in enzyme detergent producers, platinum refining workers, laboratory workers and health care workers using latex gloves. The review by Vandenplas 2010 summarises the scientific evidence on sensitiser-induced occupational asthma and rhinitis that has been published during the past five years. It includes the findings

and recommendations of the above-mentioned reviews by EAACI Task Force on Occupational Rhinitis (EAACI 2008; Moscato 2009). From the above, it appears that to date, there has not been a Cochrane review that assesses the effect of workplace interventions on the incidence and severity of work-related rhinitis and rhinosinusitis. However, there is one Cochrane review that deals with pre-employment examinations for preventing occupational injury and disease in workers (Mahmud 2010). There is another Cochrane review on prevention of respiratory tract symptoms, infections and asthma by remediating buildings damaged by dampness and mould (Sauni 2015). Because the focus of these two published Cochrane reviews is at least partly the same as in our review, we will exclude studies on pre-employment examinations and building remediations (Mahmud 2010; Sauni 2015) from our review on primary prevention of WRR or WRRS. Another review in progress will examine the effects of workplace interventions as a treatment for WRR and WRRS.

OBJECTIVES To assess the effects of interventions aimed at preventing the onset of WRR and WRRS in occupational settings. We will combine findings of rhinitis and rhinosinusitis in this review due to their similarity in definition, presentation and reported effects, but we will separate the two entities if possible in our subgroup analysis.

METHODS

Criteria for considering studies for this review

Types of studies For inclusion in our review, we will consider all randomised controlled trials and quasi-randomised controlled trials that have assessed the effectiveness of interventions to prevent the onset of WRR and WRRS in occupational settings. Since many intervention studies are conducted on a group level (often preventing a proper randomisation process), we will also consider controlled before-and-after (CBA) studies with at least two interventions and two control sites, as well as interrupted time-series (ITS) studies with at least three data points before and after the intervention (according to the criteria of the Cochrane Effective Practice and Organisation of Care Group; EPOC 2014). We will include studies reported as full-text, those published as abstract only and unpublished data.


3

Types of participants We will include adult workers (aged 16 and above) of both sexes with a history of exposure to the various potential aetiological agents for WRR and WRRS at the workplace and who have not sought medical help for rhinitis or rhinosinusitis. These participants will be predominantly asymptomatic, although a small proportion (10% or less) may have some symptoms relating to the above illnesses that have not been severe enough to lead to medical attention.

Types of interventions We will include studies aimed at preventing WRR and WRRS among workers. Primary preventive interventions (excluding preemployment examinations and studies on remediating buildings damaged by dampness and mould) will be classified as follows. • Elimination or substitution of the sensitising agent. • Engineering controls to maintain safe working conditions and limit exposure to sensitisers and irritants. ◦ Process enclosure ◦ Ventilation ◦ Process or equipment modification ◦ Isolation of work activities involving allergens or irritants, or isolation of worker to a work area with no exposure ◦ Other • Administrative controls. ◦ Job rotation ◦ Rest periods ◦ Screening the workforce at risk • Training and education for management and staff • Personal protective equipment (for the worker). ◦ Respiratory protection ◦ Other personal protective devices We will include studies that compare one or more of the above with no intervention or other types of intervention.

Types of outcome measures

Primary outcomes

We will include studies reporting data on rhinitis or rhinosinusitis symptoms. For these symptoms, we will consider the following options as outcome measurements. • Diagnosis based on interview and clinical examination by a physician, based on the following criteria. ◦ Exposure to causes and conditions at the work environment that are known to cause rhinitis or to exacerbate pre-existing rhinitis (Moscato 2009). ◦ Intermittent or persistent symptoms of rhinitis, including nasal congestion, sneezing, rhinorrhoea, itching,

variable nasal airflow limitation, hypersecretion, or a combination of any of these, which begin and endure when the person is in a particular work environment and which cannot be attributed to exposure to sensitising agents outside the workplace (Moscato 2009). ◦ Ruling out of conditions that may present with symptoms similar to rhinitis, such as structural or mechanical factors like deviated nasal septum, inflammatory or immunological conditions like nasal polyps or systemic lupus erythomatosus, or cerebralspinal fluid rhinorrhoea (Dykewicz 1998; Dykewicz 2010). • Physician’s diagnosis as reported by workers. • Rhinitis or rhinosinusitis symptoms collected by a validated questionnaire. • Medication(s) prescribed for rhinitis or rhinosinusitis. The timing of these measurements will be determined by the authors of the individual studies. We will group them in logical intervals, such as less than three months after the intervention, between three months and six months after, between six months and 12 months after, and 12 months or more after the intervention.

Secondary outcomes

1. Measurement of exposure to allergens or irritants (personal, environmental or both) by any valid objective measurementassuming that if exposure is lower, the likelihood of developing WRR and WRRS will also be reduced 2. Nasal hyperresponsiveness, measured using objective and validated tools such as intranasal cold dry air provocation (Braat 1998) or short-time cold dry air exposure (Van Gerven 2012) 3. Loss of productivity measured as lost workdays 4. Cost of treatment Reporting one or more of the secondary outcomes listed here in the trial is not an inclusion criterion for the review.

Search methods for identification of studies

Electronic searches We will conduct a systematic literature search to identify all published and unpublished trials that can be considered eligible for inclusion in this review. We will adapt the search strategy we developed for PubMed (see Appendix 1) for use in the other electronic databases. The literature search will identify potential studies in all languages. We will translate the non-English language papers and fully assess them for potential inclusion in the review as necessary. We will search different electronic databases in order to identifypotential studies, including: • Cochrane Central Register of Controlled Trials (CENTRAL) (Wiley Online Library);


4

• • • • • • •

MEDLINE (PubMed) (Appendix 1); EMBASE; PsycINFO (ProQuest); NIOSHTIC (OSH-UPDATE); NIOSHTIC-2 (OSH-UPDATE); HSELINE(OSH-UPDATE); CISDOC (OSH-UPDATE).

We will also conduct a search of ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization trials portal (www.who.int/ ictrp/en/). We will search all databases from their inception to the present, imposing no restriction on language of publication. Searching other resources We will handsearch reference lists of all primary studies and review articles for additional references. We will contact experts in the field to identify additional unpublished materials.

3. Interventions: description of intervention, comparison, duration, intensity, content of both intervention and control condition, and cointerventions. 4. Outcomes: description of primary and secondary outcomes specified and collected, and time points reported. 5. Notes: funding for trial and notable conflicts of interest of trial authors. Two review authors (SKB, ZAM) will independently extract outcome data from included studies. We will note in the ’Characteristics of included studies’ table if outcome data was not reported in a usable way. We will resolve disagreements by consensus or by involving a third review author (LA or TJH). One review author (MYA) will transfer data into the Review Manager (RevMan 2014) file. We will double check that data is entered correctly by comparing the data presented in the systematic review with the study reports. A second review author (MA) will spot check study characteristics for accuracy against the trial report.

Assessment of risk of bias in included studies

Data collection and analysis

Selection of studies Two pairs of review authors (MAK, NAM and LA, IH) will independently screen titles and abstracts to examine all the potential studies we identify as a result of the search and code them as ’retrieve’ (eligible or potentially eligible/unclear) or ’do not retrieve’. We will retrieve the full-text study reports/publications, and two pairs of review authors (SKB, ZAM and MYA, MA) will independently screen the full text and identify studies for inclusion, identifying and recording reasons for excluding the ineligible studies. We will resolve any disagreement through discussion, and if required, we will consult a third review author (SM). We will identify and exclude duplicates and collate multiple reports of the same study so that each study rather than each report is the unit of interest in the review. We will record the selection process in sufficient detail to complete a PRISMA flow diagram (Moher 2009) and a ’Characteristics of excluded studies’ table. Data extraction and management We will use a data collection form for study characteristics and outcome data, which will have been piloted on at least one study in the review. Two review authors (MFB, NAM) will extract study characteristics from included studies. We will extract the following study characteristics. 1. Methods: study design, total duration of study, study location, study setting, withdrawals study period. 2. Participants: N, mean age or age range, gender, severity of condition, diagnostic criteria if applicable, inclusion criteria and exclusion criteria.

Two review authors (NAM, NM) will independently assess risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will resolve any disagreements by discussion or by involving another author (SM). We will assess the risk of bias in included RCTs according to the following domains. 1. Random sequence generation. 2. Allocation concealment. 3. Blinding of participants and personnel. 4. Blinding of outcome assessment. 5. Incomplete outcome data. 6. Selective outcome reporting. 7. Other bias. We will grade each potential source of bias as high, low or unclear and provide a quote from the study report together with a justification for our judgment in the ’Risk of bias’ table. We will summarise the risk of bias judgements across different studies for each of the domains listed. We will consider blinding separately for different key outcomes where necessary (e.g. for unblinded outcome assessment, risk of bias for all-cause mortality may be very different than for a patient-reported pain scale). Where information on risk of bias relates to unpublished data or correspondence with the investigators of the research articles, we will note this in the ’Risk of bias’ table. We will consider RCTs to have an overall high risk of bias if we judge them to have a high risk of bias in domains 1, 2 and 5. For CBA, we will use domains 3 to 7 from above with two additional criteria developed by Cochrane Risk Of Bias Assessment Tool for Non-Randomised Studies of Interventions (ACROBATNRSI) group (Sterne 2014), which are: 1. bias due to confounding; and 2. bias in selection of participants into the study.


5

We will consider CBAs to have an overall high risk of bias if we judge them to have a high risk of bias in the above two domains and domain 5 from the previous list. For ITS studies, we will use the quality criteria developed by the Cochrane EPOC Review Group (EPOC 2014). The quality assessment criteria for ITS designs consists of: 1. protection against secular changes (three items); 2. protection against detection bias (two items); 3. completeness of data set (one item); and 4. reliable primary outcome measures (one item). We will answer each item as ’done’, ’not clear’ or ’not done’. When considering treatment effects, we will take into account the risk of bias for the studies that contribute to that outcome. We will conduct the review according to this published protocol and report any deviations from it in the ’Differences between protocol and review’ section of the systematic review. Measures of treatment effect We will enter the outcome data for each study into the data tables in RevMan (RevMan 2014) to calculate the treatment effects. We will use risk ratio and risk difference for dichotomous outcomes, and mean differences or standardised mean differences for continuous outcomes, or other type of data as reported by the authors of the studies. If only effect estimates and their 95% confidence intervals or standard errors are reported in studies, we will enter these data into RevMan using the generic inverse variance method. We will ensure that higher scores for continuous outcomes have the same meaning for the particular outcome, explain the direction to the reader and report where the directions were reversed if this was necessary. When the results cannot be entered as detailed here, we will describe them in the ’Characteristics of included studies’ table or enter the data into additional tables. Unit of analysis issues For studies that employ a cluster-randomised design and report sufficient data to be included in the meta-analysis, but which do not make an allowance for the design effect, we will calculate the design effect based on a fairly large assumed intracluster correlation of 0.10. We base this assumption of 0.10 being a realistic estimate by analogy on studies about implementation research (Campbell 2001). We will follow the methods stated in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) for the calculations. Dealing with missing data We will contact investigators or study sponsors in order to verify key study characteristics and obtain missing numerical outcome data where possible (e.g. when a study is identified as abstract only). Where this is not possible, and the missing data are thought to introduce serious bias, we will explore the impact of including

such studies in the overall assessment of results by a sensitivity analysis. If numerical outcome data (such as standard deviations or correlation coefficients) are missing and cannot be obtained from the authors, we will calculate them from other available statistics such as P values according to the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Assessment of heterogeneity We will assess the clinical homogeneity of the results of included studies based on similarity of population, intervention, outcome and follow-up. We will consider populations as similar when they are exposed to similar aetiological cause(s) at the workplace with outcomes measured in similar ways as stated in Types of outcome measures. We will consider interventions as similar when they fall into the same category as mentioned in Types of interventions above. We will consider outcomes as similar when they are measured at similar time points, such as short-term (up to three months), medium term (between three months and a year) and long term (more than a year). We will visually inspect the data to look for heterogeneity and try to identify sources of heterogeneity among the studies. We will then decide whether it is sensible to combine the studies in a single meta-analysis. If we decide to combine the studies, we will use the Cochrane Q test to examine statistical heterogeneity between studies and Higgins’ I² statistic to assess variability in estimates of effect due to heterogeneity. We will consider a value greater than 75% to represent significant heterogeneity (Higgins 2011). When I² is higher than 75%, we will not pool results of studies in metaanalyses. Assessment of reporting biases If we are able to pool more than five trials in any single meta-analysis, we will create and examine a funnel plot to explore possible small study biases. Data synthesis We will pool data from studies judged to be clinically homogeneous using RevMan software (RevMan 2014). If more than one study provides usable data in any single comparison, we will perform a meta-analysis. When studies are statistically heterogeneous, we will use a random-effects model; otherwise we will use a fixedeffect model. When using the random-effects model, we will conduct a sensitivity check by using the fixed-effect model to reveal differences in results. We will include a 95% confidence interval (CI) for all estimates. We will describe skewed data reported as medians and interquartile ranges. Where multiple trial arms are reported in a single trial, we will include only the relevant arms. If two comparisons are combined


6

in the same meta-analysis, we will halve the control group to avoid double-counting.

Subgroup analysis and investigation of heterogeneity We plan to carry out the following subgroup analyses for the outcomes with a sufficient number of studies available. We will consider all studies that share similar exposures, and group studies that employ different categories of intervention, as detailed in Assessment of heterogeneity, into different subgroups. Some examples of different categories of interventions that we will consider in our review include: i) elimination or substitution of the sensitising agents; ii) engineering controls; iii) administrative controls; iv) training and education for the worker; and v) personal protective equipment. In addition, we will conduct subgroup analyses if data are available based on the targeted outcome of rhinitis versus rhinosinusitis. We will use the test of subgroup differences to assess the difference in the effects of the intervention across different subgroups, with a P value of less than 0.05 indicating a statistically significant difference between the subgroups compared (Borenstein 2008).

Sensitivity analysis We will perform sensitivity analyses for the primary outcomes and any secondary outcomes with sufficient number of studies included to assess the robustness of our findings,excluding studies with high risk of bias. We will follow our criteria in judging RCTs and non-RCTs to have an overall high risk of bias as detailed in Assessment of risk of bias in included studies.

Summary of findings table We will create a ’Summary of findings’ table using all five outcomes as mentioned under ’Types of outcome measures’ above. We will use the five GRADE considerations (study limitations, consistency

of effect, imprecision, indirectness and publication bias) to assess the quality of the body of evidence as it relates to the prespecified outcomes. We will use methods and recommendations described in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) using a web-based version of the GRADEpro software. We will justify all decisions to downgrade or upgrade the quality of studies using footnotes, and we will make comments to aid readers’ understanding of the review where necessary. Reaching conclusions We will base our conclusions only on findings from the quantitative or narrative synthesis of included studies for this review. We will avoid making recommendations for practice because such recommendations would be based on more than just the evidence, such as values and available resources. Our implications for research will suggest priorities for future research and outline what the remaining uncertainties are in the area.

ACKNOWLEDGEMENTS We would like to thank the Director General of Health Malaysia for permission to publish. Our appreciation goes to Professor Dr Jacqueline Ho and Dr Nai Ming Lai for their continuous guidance in developing this protocol. We thank Jani Ruotsalainen, Managing Editor, Cochrane Work Group for providing administrative and logistical support for the conduct of the current review, and Kaisa Neuvonen, Trials Search Co-ordinator, Cochrane Work Group for developing and executing the search strategies. We also thank the Cochrane Work Group’s Co-ordinating Editor Jos Verbeek, Managing Editor Jani Ruotsalainen, Editor Riitta Sauni and external peer referees Claire Hopkins, Carl Philpott and Irmeli Lindström for their comments. Finally, we thank Meggan Harris for copy editing the text.

REFERENCES

Additional references Ameille 2013 Ameille J, Hamelin K, Andujar P, Bensefa-Colas L, Bonneterre V, Dupas D, et al. Occupational asthma and occupational rhinitis: the united airways disease model revisited. Occupational and Environmental Medicine 2013; 70(7):471–5. Balkissoon 2002 Balkissoon R. Occupational upper airway disease. Clinics in Chest Medicine 2002;23:717–25.

Borenstein 2008 Borenstein M, Hedges LV, Higgins JPT. Introduction to Meta-analysis. Chicester (UK): John Wiley and Sons, 2008. Braat 1998 Braat JPM, Mulder PG, Fokkens WJ, VanWijk RG, Rijntjes E. Intranasal cold dry air is superior to histamine challenge in determining the presence and degree of nasal hyperreactivity in nonallergic noninfectious perennial rhinitis. American Journal of Respiratory and Critical Care Medicine June 1998;157(6):1748–55.


7

Calderon 2007 Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/ 14651858.CD001936.pub2] Campbell 2001 Campbell MK, Mollison J, Grimshaw JM. Cluster trials in implementation research: estimation of intracluster correlation coefficients and sample size. Statistics in Medicine 2001;20(3):391–9. Chan 2009 Chan Y, Kuhn FA. An update on the classifications, diagnosis, and treatment of rhinosinusitis. Current Opinion in Otolaryngology & Head and Neck Surgery 2009;17:204–8. Cheng 2006 Cheng J, Yang XN, Liu X, Zhang SP. Capsaicin for allergic rhinitis in adults. Cochrane Database of Systematic Reviews 2006, Issue 2. [DOI: 10.1002/ 14651858.CD004460.pub2] Crystal-Peters 2000 Crystal-Peters J, Crown WH, Goetzel RZ, Schutt DC. The cost of productivity losses associated with allergic rhinitis. American Journal of Managed Care 2000;6(3):373–8. Curti 2012 Curti S, Mattioli S, Baldasseroni A, Farioli A, Zanardi F, Lodi V, et al. Interventions for primary prevention of occupational asthma. Cochrane Database of Systematic Reviews 2012, Issue 3. [DOI: 10.1002/ 14651858.CD009674] Dressel 2007 Dressel H, Gross C, De la Motte D, Sultz J, Jorres RA, Nowak D. Educational intervention decreases exhaled nitric oxide in farmers with occupational asthma. The European Respiratory Journal 2007;30(3):545–8. Dykewicz 1998 Dykewicz MS, Fineman S, Skoner DP, Nicklas R, Lee R, Blessing-Moore J, et al. Diagnosis and management of rhinitis: complete guidelines of the joint task force on practice parameters in allergy, asthma and immunology. American Academy of Allergy, Asthma, and Immunology. Annals of Allergy, Asthma and Immunology November 1998; 81(5 Pt 2):478-518. Dykewicz 2010 Dykewicz MS, Hamilos DL. Rhinitis and sinusitis. The Journal of allergy and clinical immunology 2010;125(2 Suppl 2):S103–15. [PUBMED: 20176255]

workers exposed to laboratory animals. Occupational and Environmental Medicine 2005;62(11):766–71. EPOC 2014 Cochrane Effective Practice and Organisation of Care Review Group. EPOC resources for review authors. http:// epoc.cochrane.org/epoc-resources-review-authors (accessed 30 November 2014). Fokkens 2012 Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. European position paper on rhinosinusitis and nasal polyps 2012. Rhinology. Supplement 2012;23(3): 1–298. [PUBMED: 22764607] Fujita 2006 Fujita H, Ogawa M, Endo Y. A case of occupational bronchial asthma and contact dermatitis caused by orthophthalaldehyde exposure in a medical worker. Journal of Occupational Health 2006;48(6):413–6. [PUBMED: 17179633] Gautrin 2001 Gautrin D, Ghezzo H, Infante-Rivard C, Malo JL. Natural history of sensitization, symptoms and occupational diseases in apprentices exposed to laboratory animals. The European Respiratory Journal 2001;17(5):904–8. Harvey 2007 Harvey R, Hannan SA, Badia L, Scadding G. Nasal saline irrigations for the symptoms of chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2007, Issue 3. [DOI: 10.1002/14651858.CD006394.pub2] Hellgren 2008 Hellgren J. Occupational rhinosinusitis. Current Allergy and Asthma Reports 2008;8(3):234–9. Higgins 2011 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. HSE 2013 Health and Safety Executive. Personal protective equipment at work: a brief guide. www.hse.gov.uk/pubns/indg174.htm (accessed April 14 2015). Hytonen 1997 Hytonen M, Kanerva L, Malmberg H, Martikainen R, Mutanen P, Toikkanen J. The risk of occupational rhinitis. International Archives of Occupational and Environmental Health 1997;69(6):487–90.

EAACI 2008 EAACI Task Force on Occupational Rhinitis, Moscato G, Vandenplas O, Gerth Van Wijk R, Malo JL, Quirce S, et al. Occupational rhinitis. Allergy 2008;63(8):969–80. [PUBMED: 18691299]

Liss 2003 Liss GM, Tarlo SM, Doherty J, Purdham J, Greene J, McCaskell L, et al. Physician diagnosed asthma, respiratory symptoms, and associations with workplace tasks among radiographers in Ontario, Canada. Occupational and Environmental Medicine 2003;60(4):254–61. [PUBMED: 12660373]

Elliott 2005 Elliott L, Heederik D, Marshall S, Peden D, Loomis D. Incidence of allergy and allergy symptoms among

Mahmud 2010 Mahmud N, Schonstein E, Schaafsma F, Lehtola Marika M, Fassier JB, Reneman Michiel F, et al. Pre-employment


8

examinations for preventing occupational injury and disease in workers. Cochrane Database of Systematic Reviews 2010, Issue 12. [DOI: 10.1002/14651858.CD008881] Marple 2009 Marple BF, Stankiewicz JA, Baroody FM, Chow JM, Conley DB, Corey JP, et al. Diagnosis and management of chronic rhinosinusitis in adults. Postgraduate Medicine 2009;121(6): 121–39. Mishra 2012 Mishra A, Kawatra R, Gola M. Interventions for atrophic rhinitis. Cochrane Database of Systematic Reviews 2012, Issue 2. [DOI: 10.1002/14651858.CD008280.pub2; : CD008280] Moher 2009 Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Open Medicine 2009;3(3):123–30. Moscato 2009 Moscato G, Vandenplas O, Van Wijk RG, Malo JL, Perfetti L, Quirce S, et al. EAACI position paper on occupational rhinitis. Respiratory Research 2009;10:16. Nasser 2010 Nasser M, Fedorowicz Z, Aljufairi H, McKerrow W. Antihistamines used in addition to topical nasal steroids for intermittent and persistent allergic rhinitis in children. Cochrane Database of Systematic Reviews 2010, Issue 7. [DOI: 10.1002/14651858.CD006989.pub2] Nurmatov 2012 Nurmatov U, Van Schayck CP, Hurwitz B, Sheikh A. House dust mite avoidance measures for perennial allergic rhinitis: an updated Cochrane systematic review. Allergy 2012;67 (2):158–65. Radulovic 2010 Radulovic S, Calderon Moises A, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis. Cochrane Database of Systematic Reviews 2010, Issue 12. [DOI: 10.1002/14651858.CD002893.pub2] RevMan 2014 The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. Sacks 2011 Sacks PL, Harvey Richard J, Rimmer J, Gallagher RM, Sacks R. Topical and systemic antifungal therapy for the symptomatic treatment of chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2011, Issue 8. [DOI: 10.1002/14651858.CD008263.pub2] Sakunkoo 2012 Sakunkoo P, Laopaiboon M, Koh D. Behavioural interventions for promoting respiratory protection use in workers. Cochrane Database of Systematic Reviews 2012, Issue 10. [DOI: 10.1002/14651858.CD010157]

Sarlo 2003 Sarlo K. Control of occupational asthma and allergy in the detergent industry. Annals of Allergy, Asthma and Immunology 2003;90(5 Suppl 2):32–4. Sauni 2015 Sauni R, Verbeek Jos H, Uitti J, Jauhiainen M, Kreiss K, Sigsgaard T. Remediating buildings damaged by dampness and mould for preventing or reducing respiratory tract symptoms, infections and asthma. Cochrane Database of Systematic Reviews 2015, Issue 2. [DOI: 10.1002/ 14651858.CD007897.pub3] Scadding 2008 Scadding GK, Durham SR, Mirakian R, Jones NS, Leech SC, Farooque S, et al. British Society for Allergy and Clinical Immunology. BSACI guidelines for the management of allergic and non-allergic rhinitis. Clinical and Experimental Allergy 2008;38:19–42. Schweigert 2000 Schweigert MK, Mackenzie DP, Sarlo K. Occupational asthma and allergy associated with the use of enzymes in the detergent industry-a review of the epidemiology, toxicology and methods of prevention. Clinical & Experimental Allergy 2000;30(11):1511–8. Siracusa 2000 Siracusa A, Desrosiers M, Marabini A. Epidemiology of occupational rhinitis: prevalence, aetiology and determinants. Clinical and Experimental Allergy 2000;30 (11):1519–34. [PUBMED: 11069559] Slavin 2010 Slavin RG. Update on occupational rhinitis and asthma. Allergy and Asthma Proceedings 2010;31(6):437–43. [PUBMED: 21708054] Sterne 2014 Sterne J, Higgins J, Reeves BC. A Cochrane Risk Of Bias Assessment Tool: for Non-Randomised Studies of Interventions (ACROBAT-NRSI). http:// www.riskofbias.info (accessed 18 March 2015). Taramarcaz 2003 Taramarcaz P, Gibson Peter G. Intranasal corticosteroids for asthma control in people with coexisting asthma and rhinitis. Cochrane Database of Systematic Reviews 2003, Issue 3. [DOI: 10.1002/14651858.CD003570] Van Gerven 2012 Van Gerven L, Boeckxstaens G, Jorissen M, Fokkens W, Hellings PW. Short-time cold dry air exposure: a useful diagnostic tool for nasal hyperresponsiveness. Laryngoscope 2012;122(12):2615–20. [PUBMED: 22865676] Vandenplas 2010 Vandenplas O, Dramaix M, Joos G, Louis R, Michils A, Verleden G, et al. The impact of concomitant rhinitis on asthma-related quality of life and asthma control. Allergy 2010;65(10):1290–7. Wright 2014 Wright LS, Phipatanakul W. Environmental remediation in the treatment of allergy and asthma: latest updates. Current


9

Allergy and Asthma Reports 2014;14(3):419. [PUBMED: 24488258] Zacharek 2004 Zacharek MA, Hwang PH, Fong KJ. The office management of recalcitrant rhinosinusitis. Otolaryngologic Clinics of North America 2004;37:365–79. Zhao 2012 Zhao YA, Shusterman D. Occupational rhinitis and other work-related upper respiratory tract conditions. Clinics in Chest Medicine 2012;33:637–47. ∗ Indicates the major publication for the study

APPENDICES

Appendix 1. MedLine Search Strategy (PubMed)

1

Search rhinitis[Title/Abstract]

2

Search rhinitis[MeSH Terms]

3

Search rhinosinusitis[Title/Abstract]

4

Search sinusitides[MeSH Terms]

5

Search (#1 OR #2 OR #3 OR #4)

6

Search work[Title/Abstract]

7

Search workplace[Title/Abstract]

8

Search work-related[Title/Abstract]

9

Search workplace[MeSH Terms]

10

Search environment*[Title/Abstract]

11

Search environment[MeSH Terms]

12

Search employment[Title/Abstract]

13

Search employment[MeSH Terms]

14

Search occupation*[Title/Abstract]


10

(Continued)

15

Search air pollutants, occupational[MeSH Terms]

16

Search disease, occupational[MeSH Terms]

17

Search exposure, occupational[MeSH Terms]

18

Search (#6 OR #7 OR #8 OR #9 OR #10 Or #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17

19

Search (#5 AND #18)

20

Search randomized controlled trial [pt]

21

Search controlled clinical trial [pt]

22

Search randomized [tiab]

23

Search placebo [tiab]

24

Search clinical trials as topic [mesh: noexp]

25

Search randomly [tiab]

26

Search trial [ti]

27

Search (#20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26)

28

Search (animals [mh] NOT humans [mh])

29

Search (#27 NOT #28)

30

Search (#19 AND #29)

CONTRIBUTIONS OF AUTHORS Conceiving the protocol: SKB & ZAM Designing the protocol: NAM, MYA, MA, LA, IH & TJH Coordinating the protocol: SKB, ZAM & MAK Designing search strategies: SKB, ZAM, MAK, NM, NAM, MYA, MA, SM & TJH in collaboration with Cochrane Work Group Trials Search Co-ordinator Kaisa Neuvonen Writing the protocol: SKB, ZAM, MAK, NM, NAM, MYA, MA, LA, IH, SM, MFB & TJH Providing general advice on the protocol: LA, IH, SM, MFB & TJH Performing previous work that was the foundation of the current study: NAM, MFB


11

DECLARATIONS OF INTEREST Sophia K Bakon: None known Zuraifah Asrah Mohamad: None known Nor Asiah Muhamad: None known Masita Arip: None known Mohd Yusoff Adon: None known Iskandar Hailani: None known Liisa Airaksinen: None known Shahnaz Murad: None known Muhammad A Kamaluddin: None known Mohamed Faizal Bakhtiar: None known Timo J Hannu: Dr Timo Hannu owns 150 shares (share class B) of Orion Corporation, a European pharmaceuticals and diagnostics company. In 2011, he received an honorarium of GBP 200 for writing a review entitled “Reactive arthritis”, which was published in the journal Best Practice & Research Clinical Rheumatology.


12