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Background In Swedish working life, exposure to cold and exposure to hand-arm vibration (HAV) are two common health hazards. Health effects of HAV in the neurosensory, vascular and musculoskeletal systems are collectively denoted hand-arm vibration syndrome (HAVS), and have been thoroughly studied. Effects of cold exposure in terms of effects on the peripheral neurosensory and vascular system are on the contrary limited, especially in an occupational setting. Effects of cold exposure or cold injury have not previously been assessed with quantitative sensory testing (QST). Commonly reported symptoms after exposure to HAV and after cold injuries, includes cold sensitivity and sensation of cold. Cold sensitivity can also occur without previous exposure to vibration or cold and may have a major impact on quality of life. Other possible risk factors for cold sensitivity need to be assessed. Sensation of cold hands could theoretically imply an early manifestation of damage to the neurosensory or vascular system, and therefore be of importance to enable early detection of vascular and neurosensory HAVS. The purpose of this thesis was to increase the knowledge about health effects from cold and HAV on the peripheral neurosensory and vascular system, with an occupational perspective. The aims were: first, to identify and evaluate health effects and sequelae in the peripheral neurosensory and vascular system due to cold injury and cold exposure; second, to investigate if sensation of cold hands is a predictor for future onset of Raynaud's phenomenon or paresthesia; and third, to identify possible risk factors associated with cold sensitivity.

Methods A case series on 15 military conscripts with local cold injuries in the hands or feet, involving QST and symptom descriptions, was conducted to investigate the hypothesis that cold injuries can result in similar neurosensory and vascular impairments as in HAVS. To assess health effects of cold exposure, a cohort study on 54 military conscripts in cold winter military training, with cold exposure assessments, was conducted. Possible health effects were assessed after 14 months of military training, containing considerable cold exposure, by means of QST, Finger systolic blood pressure after local cooling (FSBP) and a questionnaire. To investigate if sensation of cold hands is a predictor for vascular or neurosensory HAVS we investigated a cohort of 178 employees at a manufacturing company where HAV was a common exposure. The cohort was followed during 21 years and both vibration exposure and health outcomes were assessed regularly. Questionnaire items were used to assess sensations of cold hands as well as signs of Raynaud’s phenomenon and paresthesia. To identify risk factors for cold sensitivity a case-control study was conducted involving 997iiiparticipants from the general population in northern Sweden. The study was cross-sectional and explored possible risk factors for cold sensitivity.

Results Cold injuries and cold exposure were associated with reduced sensibility in QST and increase severity and prevalence of neurosensory and vascular symptoms. Our results did not show any impairment in peripheral blood flow due to cold exposure, detectable by FSBP. The risk of developing Raynaud's phenomenon was increased for workers previously reporting sensation of cold hands (OR 6.3, 95% CI 2.3-17.0). No increased risk for paresthesia in relation to a sensation of cold hands was observed. The identified risk factors for cold sensitivity were frostbite in the hands, rheumatic disease, nerve injury in upper extremities or neck, migraine and vascular disease. When analysing women and men separately, women’s risk factors were frostbite in the hands, rheumatic disease, migraine and cold exposure. Men’s risk factors were frostbite in the hands, vibration exposure and nerve injury in upper extremities or neck. BMI > 25 was a protective factor for both men and women.

Conclusion Cold injury and cold exposure are associated with impairments in the neurosensory system, detectable by QST. Symptoms such as sensation of cold hands and white fingers indicate vascular involvement, even though no vascular impairments due to cold exposure could be detected by objective measurements. A sensation of cold hands is a risk factor for development of Raynaud´s phenomenon, but not for paresthesia. At the individual level, reporting cold hands does not appear to be useful information when considering the possibility of a future development of Raynaud’s phenomenon. Frostbite in the hands is a risk factor for cold sensitivity among both women and men. For women rheumatic disease, migraine and cold exposure are also independent risk factors, and for men, exposure to HAV. Being overweight is a protective factor for both women and men.

Background: Living in a cold climate is associated with several adverse health effects. The main purpose of this thesis was to describe cold exposure characteristics in northern Sweden, and investigate the associations between such exposure and the reporting of neurological and vascular hand symptoms. One common cold-related hand symptom is Raynaud’s phenomenon, defined as episodic attacks of acral pallor or cyanosis. There is evidence to suggest that cold exposure can act both as a causal factor and a trigger for such vasospastic symptoms. Other important associated factors include exposure to hand-arm vibration and the presence of rheumatic disease. A somewhat similar clinical entity, cold sensitivity, is defined as a collection of acquired symptoms, resulting in an abnormal aversion to cold, with pain, sensory alterations, stiffness, or color changes, which may occur after a traumatic injury. The condition is hypothesized to mainly originate from nerve injury. The effects of cold exposure on hand function, the occurrence of cold sensitivity in the general population, the link between cold exposure and cold sensitivity, as well as the interface between cold sensitivity and Raynaud’s phenomenon are not fully understood. Therefore, this thesis was also intended to expand the knowledge on Raynaud’s phenomenon and cold sensitivity.

Methods: Postal surveys were sent to a sample of men and women between 18 and 70 years of age, living in Norrbotten, Västerbotten, Västernorrland, and Jämtland, drawn from the national Swedish population register. The first survey collected data on 12,627 subjects, and the results were used to describe cold exposure characteristics, and broadly investigate the statistical associations with different neurological and vascular hand symptoms (Paper I). A follow-up survey was sent to a subset of responders, to form nested case–control studies on cold sensitivity (N=1,230; Paper II) and Raynaud’s phenomenon (N=1,400; Paper III). Subjects with cold sensitivity (N=12) from Paper II were subsequently recruited to a laboratory study, to investigate the vascular and neurosensory function of the hands, by means of physical examination, laser speckle contrast analysis before and after cold stress testing, and thermal quantitative sensory testing (Paper IV). Finally, healthy controls (N=1,239) from the case–control studies were used as a reference population for the Cold intolerance symptom severity questionnaire, to establish a cut-off for abnormal cold sensitivity (Paper V).

Results: In Paper I, cold exposure was commonly reported, both during work and leisure time. Exposure was most pronounced in alpine regions, generally higher among men than women, and decreased with age. Highly cold-exposed occupational groups were militaries; agricultural, forestry and fishery workers; and crafts and related trades workers (e.g. construction workers). The correlation between occupational and leisure-time cold climate exposure was low. Men reported more occupational exposure to hand-arm vibration than women, but the correlation between occupational cold and vibration exposure was low. A range of neurological and vascular hand symptoms were statistically associated with high cold exposure, such as decreased perception to touch, warmth, and cold, as well as Raynaud’s phenomenon. In Paper II, cold sensitivity was significantly associated with previous frostbite affecting the hands, rheumatic disease, upper extremity nerve injury, migraine, vascular disease, and high body mass index (inversely), in a multiple conditional logistic regression model. In Paper III, Raynaud’s phenomenon was significantly associated with previous frostbite affecting the hands, first degree heredity, and high body mass index (inversely), in a similar model. Previous upper extremity nerve injury was suggested as a separating trait between Raynaud’s phenomenon and cold sensitivity. In Paper IV, laser speckle contrast analysis indicated disturbances in microvascular regulation, while physical examination and thermal quantitative sensory testing mainly yielded normal results. In Paper V, the 95th percentile for the Cold intolerance symptom severity score was 49.5 for men, and 53.0 for women.

Conclusions: Cold exposure in the working-age population of northern Sweden varied with age, gender, occupation, and place of residence. Cold exposure was related to the reporting of neurological and vascular hand symptoms in the population as a whole. There was a major overlap between reporting cold sensitivity and Raynaud’s phenomenon, and the conditions shared several associated factors. Previous upper extremity nerve injury was suggested to be a separating trait, supporting the neurosensory pathophysiological hypothesis for cold sensitivity. Cold sensitivity was not effectively assessed by physical examination or thermal quantitative sensory testing. However, laser speckle contrast analysis could prove a useful tool in further studies on cold sensitivity. A Cold intolerance symptom severity score above 50 could be considered to indicate abnormal cold sensitivity, and be used to guide further care.