Cigarettes Have a Negative Effect on Wound Healing of Diabetic Foot Ulcers – meta-analysis of 18 studies

Abstract

Diabetic foot ulcers (DFUs) have a complex pathophysiology and require an expert multidisciplinary treatment. There are several, both systemic and local, risk factors for DFUs. A recent meta-analysis of 18 studies has now provided robust evidence on the detrimental effect of smoking on healing of DFUs. Indeed, healing rates were consistently lower among smokers than among nonsmokers. Based on this new evidence, it is reasonable to consider the utility of smoking cessation programs. Incorporation of the latter into the holistic therapeutic strategy for DFUs may be anticipated to improve healing rates, but this remains to be shown.

The diabetic foot is a remarkably complex condition: many parameters such as peripheral neuropathy, infection, peripheral arterial disease, foot deformity, age, gender, diabetes duration, body mass index, retinopathy, nephropathy, edema, glycated hemoglobin, foot self-care habits, or smoking have been identified as risk factors.15 Although some of these factors are associated with amputations,69 their precise contribution to impaired wound healing in the diabetic foot is poorly understood.

Moreover, it is known that wound healing is not only related to wound characteristics, such as size, depth, and severity of wounds,10,11 but also to treatment, notably off-loading or surgery.12,13 Smoking is now beginning to be recognized as an additional adverse modifiable factor that increases amputation risk.7,14 However, the exact association between smoking and poor wound healing needs further clarification.

Diabetic Foot Ulcers

In this issue of the journal, a meta-analysis including 18 studies (7 retrospective and 11 prospective) from various countries has focused on analyzing the association between cigarette smoking and diabetic foot healing.15 A significant association was found between smoking and healing of diabetic foot ulcers (P = .002), with an odds ratio (OR) of 0.70 and a 95% confidence interval (CI) of 0.56 to 0.88. Healing rates were lower in smokers (mean = 62.1%, range = 20.0% to 89.6%) than in nonsmokers (mean = 71.5%, range = 40.2% to 93.8%).15 

In subgroup analysis, the retrospective cohort group had an OR of 0.62 (95% CI = 0.41-0.95, P = .009) and the prospective cohort had an OR of 0.75 (95% CI = 0.57-0.99, P = .0064).15 This meta-analysis provides evidence for the harmful effect of smoking on healing rates of diabetic foot ulcers. In the same context, a recent study has reported that current smoking was independently associated with 30-day unplanned rehospitalization in patients with diabetic foot after adjustment for confounders (OR = 1.95, 95% CI = 1.02-3.73).16

The main strength of this study is the leave-one-out sensitivity analysis, which confirmed the robustness of the meta-analysis.15 Moreover, 18 studies with as many as 5819 subjects were included.15 So far, there has been only one analysis on the detrimental effect of smoking on diabetic foot ulcers, but it has provided rather limited evidence owing to the small number of studies included, most of them case series.17 

The limitations of this meta-analysis are the significant publication bias (the authors only included English and Chinese literature) and the moderate heterogeneity of included studies.15 Nevertheless, heterogeneity did not result from publication year, overall healing rate, or study design. An additional limitation is the presence of only 2 studies providing adjusted ORs. Finally, the authors failed to analyze the association between wound healing and passive smoking, smoking cessation, or smoking for different durations.15

Based on this new evidence on the detrimental effect of smoking on healing rates of diabetic foot ulcers,15 it is reasonable to consider the utility of smoking cessation programs. Incorporation of the latter into the multidisciplinary therapeutic strategy for the diabetic foot may be anticipated to improve healing rates, but this remains to be shown. Ideally, such programs should be combined with revascularization, infection control, orthotic devices, and adjunctive modalities.9,1820 

Successful smoking cessation is a multicomponent strategy, in which pharmacotherapy appears to be most efficacious.2124 Patients would also need education on avoiding risk factors for relapse of smoking (for instance, being around other smokers, stress, or alcohol), as well as on the other unfavorable effects of smoking (notably, peripheral arterial or heart disease and lung cancer).21,25

Conclusion

There is no robust evidence on the negative effect of smoking on healing rates of diabetic foot ulcers.15 Thus, it is important for clinicians to encourage smoking cessation. This should be expected to contribute to improved ulcer healing in the diabetic foot.

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