Relationship of Healthy Building Determinants With Musculoskeletal Disorders of the Extremities: A Systematic Review

Musculoskeletal disorders (MSDs) are a substantial societal burden and various factors affect their causation, recovery, and prognosis. Management of MSDs is complex and requires multifaceted interventions. Given the challenges of MSDs and their continued burden, it is possible that additional elements could impact these disorders that have not been fully researched, for example, indoor environmental quality. Our previous review provided preliminary evidence that healthy building determinants (HBDs) are associated with the risk of back and neck pain. However, the relationship of HBDs with extremity MSDs and general MSDs (i.e., MSDs involving multiple body regions or in which body regions were unspecified in the original reports) has not been formally studied. The purpose of this review was to conduct a systematic literature review to assess the relationship of HBDs with extremity and general MSDs (PROSPERO ID: CRD42022314832). PubMed, CINAHL, Embase, and PEDRo databases were searched through April 2022. Inclusion criteria for study eligibility were as follows: humans of ages ≥18 years, reported on one or more of eight HBDs (1. air quality and ventilation, 2. dust and pests, 3. lighting and views, 4. moisture, 5. noise, 6. safety and security, 7. thermal health, 8. water quality), and compared these HBDs with extremity MSDs or general MSDs, original research, English. Exclusion criteria were as follows: articles not published in peer-reviewed journals, full-text articles unavailable. Review procedures were conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Empirical evidence statements were developed for 33 pairwise comparisons of HBDs with MSDs. The search uncovered 53 eligible studies with 178,532 participants. A total of 74.6% (39/53) of the studies were cross-sectional and 81.1% (43/53) were fair quality. Overall, the majority of uncovered evidence indicates that HBDs are related to risk of extremity and general MSDs. Nineteen comparisons support that as HBDs worsen, the risk of MSDs increases. Six comparisons had conflicting evidence. Three comparisons support that poor HBDs are not related to increased risk of extremity and general MSDs. Five comparisons had no evidence. This systematic review builds upon previous work to provide useful starting points to enhance awareness about the HBD-MSD relationship. These findings can help inform research and public health efforts aimed at addressing suboptimal HBDs through appropriate interventions to improve the lives of those suffering from MSDs.

Approaches adapted from the Oxford Centre for Evidence-Based Medicine, Clinical Information Access Portal [20][21][22][23], and American Physical Therapy Association [8,24] were used to handle data and synthesize the evidence [13].
Study quality and level of evidence: Study quality (risk of bias) was assessed using the NIH quality assessment instrument for observational studies [32]. The instrument has 14 items in which an item is rated as yes = 1, or no = 0 (total instrument score is 0-14) [32]. The authors calculated score ranges for study quality categories [32] from the total score [13]: 0-4 = poor quality (high risk of bias), 5-9 = fair quality (between low risk and high risk of bias), 10-14 = good quality (low risk of bias) [32]. Level of evidence (study type) was categorized using approaches adapted from the Oxford Centre for Evidence-Based Medicine [20][21][22][23]. JM assessed study quality and evidence level and EG separately cross-checked the results. Subsequently, the two authors worked together until reaching a consensus about study quality and evidence level. Automation was not utilized in the processes to assess study quality and evidence level. Reporting bias was not formally assessed and the tables report missing data [13].
Evidence synthesis: Empirical evidence statements were synthesized based on strategies adapted from the Oxford Centre for Evidence-Based Medicine [21][22][23], American Physical Therapy Association [8,24], and relevant systematic reviews [13,26]. Empirical evidence statements were based on pairwise comparisons with each assessing one MSD region by one HBD category (including the three thermal health subdivisions and the aggregate variable of overall work environment). Thus, 33 pairwise comparisons were assessed: three MSD regions (upper extremity, lower extremity, general) by 11 HBD categories and subdivisions (1. air quality and ventilation, 2. dust and pests, 3. lighting and views, 4. moisture, 5. noise, 6. safety and security, 7. thermal health -uncomfortable, 8. thermal health -cold, 9. thermal health -warm, 10. water quality, and 11. overall work environment). Empirical evidence statements for the pairwise comparisons were constructed with the following categories [8], which were also used in our previous review [13]: strong evidence -"one or more level I systematic reviews support the recommendation" [8], moderate evidence -"one or more level II systematic reviews or a preponderance of level III systematic reviews or studies support the recommendation" [8], weak evidence -"one or more level III systematic reviews or a preponderance of level IV evidence supports the recommendation [8], conflicting evidence -"higher-quality studies conducted on this topic disagree with respect to their conclusions and effect" [8], or no evidence. Considering this systematic review's broad purpose and the evidence uncovered, meta-, heterogeneity-, and sensitivity analyses were not carried out.

Study Outcomes
The studies used various outcome measures for MSDs, including validated patient-reported outcomes (e.g., Nordic Musculoskeletal Questionnaire) and administrative measures (e.g., work absenteeism), as well as study-specific measures that have not been validated. Outcomes for HBDs were mainly study-specific and not validated for general use.

Empirical Evidence Statements
Evidence was uncovered in support of significant relationships between many HBD categories and subcategories with extremity and general MSDs as detailed in Table 1. For 19 pairwise comparisons, weak evidence supports a relationship indicating that poor HBDs are related to an increased risk of extremity and general MSDs. For example, this review found that poor air quality at work is related to increased risk of upper extremity MSDs [51,57,71,77]. On contrary, for three comparisons, weak evidence indicates that poor HBDs are not related to an increased risk of extremity and general MSDs. For example, this review found that poor lighting at work is not associated with increased risk of lower extremity MSDs [61,62,66]. Conflicting evidence was found for six comparisons. For example, this review found conflicting evidence regarding the relationship between uncomfortably warm temperatures at work or nonspecific locations and increased risk of upper extremity MSDs. Some studies or analyses within studies support this relationship [41,42,46,74], while others do not [40][41][42]59,74]. No evidence was found for five comparisons.

Upper extremity MSDs Lower extremity MSDs General MSDs
Air quality and ventilation Poor air quality at work is related to increased risk of UE MSDs. Evidence: weak -yes [51,57,71,77]. No [49,77].
Poor air quality at work is related to increased risk of general MSDs.
Dust and pests Dust complaint or exposure at work is related to increased risk of UE MSDs. Evidence: weak -yes [57,71]. No [77].
Dust exposure at work is related to increased risk of LE MSDs. Evidence: conflicting -yes [71]. No [62,71].
Dust exposure at work is related to increased risk of general MSDs.

Moisture
Uncomfortable moisture (dampness, humidity) at work is related to increased risk of UE MSDs. Evidence: weak -yes [46]. No: none.
Uncomfortable moisture (dampness, humidity) at work is related to increased risk of UE MSDs. Evidence: weak -yes [46]. No: none.
Increased noise at home or work is related to increased risk of LE MSDs. Evidence: conflicting -yes [52]. No [62,66].
Increased noise at work is related to increased risk of general MSDs.

Safety and security
Poor safety at work is related to increased risk of UE MSDs. Evidence: weak -yes [80]. No: none.

Evidence: none
Poor safety at work is related to increased risk of general MSDs.
Uncomfortable temperature at work is related to increased risk of LE MSDs.
Uncomfortably cold temperature at work or nonspecific location is related to increased risk of general MSDs.
Uncomfortably warm temperature at work or nonspecific location is related to increased risk of LE MSDs. Evidence: weak -yes [46,85]. No [62].
Uncomfortably warm temperature at work is NOT related to increased risk of general MSDs. Evidence: weak -yes [68]. No: none.

Water quality
Drinking poor quality water at nonspecific location is related to increased risk of UE MSDs. Evidence: weak -yes [44]. No: none.
Drinking poor quality water at home or nonspecific location is NOT related to increased risk of LE MSDs. Evidence: weak -yes [43,56,63]. No [43,56].
Drinking poor quality water at work is related to increased risk of general

General Interpretation
The current systematic review found 53 studies on the relationship of several HBDs with extremity and general MSDs. More than 60% (32/53) of these studies were published over the last decade and were carried out in diverse countries, settings, and populations, thus the attention given to the HBD-MSD relationship is increasing. This review builds upon our previous work to provide useful starting points about the HBD-MSD relationship. These findings can enhance awareness and help inform future research and public health efforts aimed at addressing suboptimal HBDs through appropriate interventions to improve the lives of those suffering from MSDs [13].
The awareness of the HBD-MSD relationship raised through the current review may also be useful to avoid unintended harm, particularly as the field progresses beyond its early stages. Healthy building initiatives evolved from prior efforts about the relationship between the built environment and human health, which typically have had a positive impact. However, sometimes these efforts had unintended consequences that created human harm. For example, attempts to improve the energy efficiency of buildings in the 1970s resulted in "sick building syndrome" (SBS) and its array of negative health consequences [112]. The SBS example highlights the need to focus on preventing unintended harm when transforming the built environment to optimize the management of MSDs. Learning from the past to sustain present efforts and inform the future is crucial to prevent unintended harm while raising awareness of human health within the indoor built environment.
Evidence from the current systematic review generally indicates that HBDs are related to risk of extremity and general MSDs. That is, poor HBDs are associated with increased risk of MSDs (in other words, as HBDs worsen, the risk of MSDs increases). Overall, the most consistent evidence in support of this statement was found for upper extremity and general MSDs, yet mixed evidence was found for lower extremity MSDs. When comparing the evidence across the various HBDs, consistent evidence supporting a positive relationship with higher risk of extremity and general MSDs was found for thermal health (cold), air quality and ventilation, thermal health (uncomfortable), moisture, safety and security, noise, and overall work environment. However, mixed evidence was found for dust and pests, lighting and views, thermal health (warm), and water quality.
The findings of the current review, combined with our other review examining the HBD relationship with back pain and neck pain, provide a comprehensive initial assessment of the association of numerous HBDs with a wide range of MSDs [13]. When considered together, the cumulative findings of the current review and our other review are largely consistent, particularly for back pain, neck pain, upper extremity MSDs, and general MSDs, as well as the HBDs of air quality and ventilation, moisture, thermal health (cold, uncomfortable), and overall work environment. However, inconsistencies in the evidence are noted for lower extremity MSDs, as well as the HBDs of dust and pests, lighting and views, noise, thermal health (warm), and water quality. When considering the current review and previous review together, the most studies, in terms of number of studies, were uncovered for thermal health, followed by air quality and ventilation, and lighting and views, while the fewest studies were found for safety and security.
The noted differences among the various musculoskeletal regions (e.g., upper extremity compared to lower extremity) and HBD categories and sub-categories (e.g., air quality and ventilation compared to noise) assessed in the current review are challenging to explain and require additional research. Possible explanations for these differences are factors inherent in the populations assessed. For example, most of the studies uncovered in the current review were conducted on workers whose primary job tasks involved relatively more upper extremity use compared to lower extremity. Thus, it is possible that the musculoskeletal regions required for a particular occupation may be most impacted by the built environment and the activity required within that environment.
The level of studies uncovered in this systematic review limits the ability to conduct a full-scale causality assessment using Hill's criteria [113]. Nevertheless, biological plausibility seems reasonable for several of the uncovered HBD-MSD relationships. For example, the current review and our previous review found evidence suggesting that uncomfortably cold indoor temperature was related to an increased risk of MSDs, which was not found for uncomfortably warm indoor temperature [13]. Possible explanations for these findings are that cold impedes muscle and joint movement [114,115], and people suffering from chronic MSDs are hypersensitive to cold [116,117].
Another example of biological plausibility that may help explain the relationship between HBDs and MSDs is the association of environmental tobacco smoke with MSDs, as found in two studies of this review [64,69]. As noted by Pisinger et al., tobacco smoke includes various toxic chemicals and gases, which can negatively impact musculoskeletal tissue perfusion and nutrition, and result in inadequate responses to mechanical stressors [69,118]. Moreover, tobacco smoke causes an increase in inflammatory cytokines and attenuation of chondrocyte activity, which may inhibit recovery and growth of musculoskeletal tissues [119].
Another explanation for the uncovered relationships is that HBDs are directly associated with other MSD risk factors that were not accounted for in the reviewed studies. For example, the current review and our previous review found that poor air quality was related to an increased risk of MSDs [13]. In this case, it is plausible that air quality may not be a direct marker for MSDs. Rather, air quality could be a direct marker for respiratory function, which in turn is a direct marker for MSDs. In agreement with this observation, other work suggests that poor indoor air quality contributes to tissue hypoxia [120], and is related to sick-building syndrome [121], which is associated with MSDs, such as muscle pain [121]. Moreover, disordered breathing is associated with aberrant carbon dioxide and oxygen physiology [122], and poorer functional movement quality [123], which in turn are associated with an increased risk for MSDs [122,124]. Similarly, the current review's and previous review's [13] finding that being annoyed with noise from neighbors is associated with an increased risk of extremity MSDs is likely best explained by accounting for other health and environmental aspects that were not measured but may be relevant to residents of multi-story housing units [52].

Limitations
The current systematic review has limitations that are similar to our previous review, which preclude widespread generalizability [13]. The uncovered evidence was mostly from lower-level evidence and no level 1 studies (e.g., controlled trials) were found, thus the impact of interventions targeting the HBD-MSD interface on health outcomes is unknown. Also, no evidence was uncovered for five of the 33 pairwise comparisons for the HBD-MSD relationships, and several comparisons had minimal studies to formulate empirical evidence statements. Furthermore, comparisons among the studies were challenging and metaanalysis was not viable because different outcomes were measured across the studies. Moreover, it is likely that other indoor HBDs exist and may be associated with MSDs, in addition to those assessed in this review, as well as those that may be inherent to the outdoor environment. Also, the studies did not adequately assess residential settings. Finally, the interrelationships of various HBDs and other factors, such as those reflecting what is put into the building rather than the building itself (e.g., ergonomics, wide array of biopsychosocial factors, such as HBDs), that may impact MSD development, recovery, and prognosis were not examined.

Implications for Practice and Policy
While the field examining the HBD-MSD relationship is in its infancy, the findings of this systematic review are useful for future research, development, and public health efforts aimed at attenuating the negative impact of MSDs within the indoor built environment [13]. These findings will help create awareness among various stakeholders involved with enhancing, and who may benefit from, the human-building-environment interface within the HBD-MSD domain, such as companies, employers, employees, property owners, tenants, patients, clinicians, and policymakers. For tenants, patients, and employees, enhancing the HBD-MSD domain could result in improved quality of life, function, and productivity [125]. For employers, these enhancements could improve measures related to job performance and employee retention [125,126]. For property owners, upgrades to human-building-environment interface within the HBD-MSD domain could result in financial gains [125], such as higher rental fees [16,31], enhanced tenant satisfaction and retention [13], and reduced risk of injury or poor health claims against owners and insurance companies. For policymakers, as well as organizations with ecological, social, and governance missions, implementation of practices to optimize the HBD-MSD domain can have wide-ranging impact on reducing human disability related to the built environment [13].

Future Research
Expanding on the current review's findings through future research would be valuable to inform policy and practice, and foster implementation of interventions designed to positively impact the indoor built environment by augmenting HBDs and reducing MSDs [13]. As detailed in a previous review, causality of the HBD-MSD relationships needs to be examined [13]. Interventions targeting HBDs need to be assessed for safety and effectiveness health outcomes for MSD management through level 1 studies, such as randomized controlled trials. Cost-effectiveness and return on investment measures for HBD-related products and services need to be modeled in health economic evaluations. Studies assessing the rising demand for working from home versus working in the office on MSDs would be useful [127]. Moreover, diverse biopsychosocial, demographic, ergonomic, and comorbidity factors should be assessed in terms of their effect on the HBD-MSD relationships.

Conclusions
Musculoskeletal disorders are a substantial societal burden and various factors affect their causation, recovery, and prognosis, which may include elements that have not been fully researched, such as indoor environmental quality. This review systematically examined the peer-reviewed literature on the relationship of eight HBDs with extremity and general MSDs. "toes"(MeSH Terms) OR "toes"(All Fields) OR "toe"(All Fields) OR "toe joint"(MeSH Terms) OR ("toe"{All Fields} AND "joint"{All Fields}) OR "toe joint"(All Fields) 41 "fingers"(MeSH Terms) OR "fingers"(All Fields) OR "finger"(All Fields) OR "finger joint"(MeSH Terms) OR ("finger"{All Fields} AND "joint"{All Fields}) OR "finger joint"(All Fields) 40 "hand"(MeSH Terms) OR "hand"(All Fields) OR "hands"(All Fields) OR "hand joints"(MeSH Terms) OR ("hand"{All Fields} AND "joints"{All Fields}) OR "hand joints"(All Fields) OR ("hand"{All Fields} AND "joint"{All Fields}) OR "hand joint"(All Fields) 39 "wrist"(MeSH Terms) OR "wrist"(All Fields) OR "wrists"(All Fields) OR "wrist joint"(MeSH Terms) OR ("wrist"{All Fields} AND "joint"{All Fields}) OR "wrist joint"(All Fields)
Study quality determined by the NIH quality assessment tool [32], with 14 items: 1. was the research question or objective in this paper clearly stated? 2.
Was the study population clearly specified and defined? 3. Was the participation rate of eligible persons at least 50%? 4. Were all the subjects selected or recruited from the same or similar populations (including the same time period)? Were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants? 5. Was a sample size justification, power description, or variance and effect estimates provided? 6. For the analyses in this paper, were the exposure(s) of interest measured prior to the outcome(s) being measured? 7. Was the timeframe sufficient so that one could reasonably expect to see an association between exposure and outcome if it existed? 8. For exposures that can vary in amount or level, did the study examine different levels of the exposure as related to the outcome (e.g., categories of exposure, or exposure measured as continuous variable)? 9.
Were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? 10. Was the exposure(s) assessed more than once over time? 11. Were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? 12. Were the outcome assessors blinded to the exposure status of participants? 13. Was loss to follow-up after baseline 20% or less? 14.
Were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)?  Table 2 Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.
3 Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).

3, 4 13b
Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions. 3, 4 13c Describe any methods used to tabulate or visually display results of individual studies and syntheses.
3, 4, Table 1,   Supplementary   Table 3 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.

13e
Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. 4

Study selection 16a
Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram. 4, 5, Figure 1 16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. 5, Figure 1 Study characteristics 17 Cite each included study and present its characteristics. 5, 6 Table 3 2023 Gherscovici Table 1 Discussion Discussion 23a Provide a general interpretation of the results in the context of other evidence. 8, 9 23b Discuss any limitations of the evidence included in the review. 9 23c Discuss any limitations of the review processes used. 9 23d Discuss implications of the results for practice, policy, and future research. 9 Other information Registration and protocol 24a Provide registration information for the review, including register name and registration number, or state that the review was not registered.

1, 2 24b
Indicate where the review protocol can be accessed, or state that a protocol was not prepared.