Life Extension Magazine®

Issue: Jun 2017

Pollution, Skin damage, and Dry eye

Pollution

Dietary antioxidants and ozone-induced bronchial hyperresponsiveness in adults with asthma.

Ozone exposure aggravates asthma, as has been demonstrated in both controlled exposures and epidemiologic studies. In the current double-blind crossover study, the authors evaluated the effects of dietary antioxidants (i.e., 400 IU vitamin E/500 mg vitamin C) on ozone-induced bronchial hyperresponsiveness in adult subjects with asthma. Seventeen subjects were exposed to 0.12 ppm of ozone or to air for 45 min during intermittent moderate exercise. Bronchial hyperresponsiveness was assessed with 10-min sulfur dioxide (i.e., 0.10 ppm and 0.25 ppm) inhalation challenges. Subjects who were given dietary antioxidants responded less severely to sulfur dioxide challenge than subjects given a placebo (i.e., forced expiratory volume in the 1st sec: -1.2% vs. 4.4%, respectively; peak flow: +2.2% vs. -3.0%, respectively; and mid-forced expiratory flow: +2.0% vs. -4.3%, respectively). Effects were more pronounced when subjects were grouped by response to sulfur dioxide at the screening visit. The results suggest that dietary supplementation with vitamins E and C benefits asthmatic adults who are exposed to air pollutants.

Arch Environ Health. 2001 May-Jun;56(3):242-9

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE).

BACKGROUND: Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. METHODS: This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 µm (PM10), less than 2·5 µm (PM2·5), and between 2·5 and 10 µm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. FINDINGS: The 312,944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 µg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 µg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 µg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). INTERPRETATION: Particulate matter air pollution contributes to lung cancer incidence in Europe. FUNDING: European Community's Seventh Framework Programme.

Lancet Oncol. 2013 Aug;14(9):813-22

Association between mortality and indicators of traffic-related air pollution in the Netherlands: a cohort study.

BACKGROUND: Long-term exposure to particulate matter air pollution has been associated with increased cardiopulmonary mortality in the USA. We aimed to assess the relation between traffic-related air pollution and mortality in participants of the Netherlands Cohort study on Diet and Cancer (NLCS), an ongoing study. METHODS: We investigated a random sample of 5,000 people from the full cohort of the NLCS study (age 55-69 years) from 1986 to 1994. Long-term exposure to traffic-related air pollutants (black smoke and nitrogen dioxide) was estimated for the 1986 home address. Exposure was characterised with the measured regional and urban background concentration and an indicator variable for living near major roads. The association between exposure to air pollution and (cause specific) mortality was assessed with Cox's proportional hazards models, with adjustment for potential confounders. FINDINGS: 489 (11%) of 4492 people with data died during the follow-up period. Cardiopulmonary mortality was associated with living near a major road (relative risk 1.95, 95% CI 1.09-3.52) and, less consistently, with the estimated ambient background concentration (1.34, 0.68-2.64). The relative risk for living near a major road was 1.41 (0.94-2.12) for total deaths. Non-cardiopulmonary, non-lung cancer deaths were unrelated to air pollution (1.03, 0.54-1.96 for living near a major road). INTERPRETATION: Long-term exposure to traffic-related air pollution may shorten life expectancy.

Lancet. 2002 Oct 19;360(9341):1203-9

Air pollution and heart rate variability among the elderly in Mexico City.

BACKGROUND: Suspended particles and ozone have been associated with varying degrees of cardiac autonomic dysfunction. METHODS: In Mexico City, residents from a nursing home underwent heart rate variability analysis every other day for 3 months. Indoor and outdoor PM2.5 (particulate matter less than 2.5 mm in diameter) were measured daily at the nursing home. Levels of ozone and other atmospheric pollutants were obtained from a nearby automated monitoring station. RESULTS: Of the initial 42 screened participants, 34 (81%) were followed during the study period. The 24-hour average levels of indoor PM2.5 ranged from 15 to 67 micro g/m3, and outdoor PM2.5 ranged from 9 to 87 micro g/m3. Daily 1-hour maximum ozone levels ranged from 47 to 228 ppb. After adjusting for age and heart rate, we observed a strong decrease in the high frequency component of heart rate variability and the average 24-hour concentrations of PM2.5. Participants with hypertension had considerably larger reductions in their HF-HRV (high frequency-heart rate variability) component in relation to both ozone and PM2.5 exposure. CONCLUSIONS: Our results suggest that ambient levels of PM2.5 and ozone can reduce the high-frequency component of heart rate variability in elderly subjects living in Mexico City and that subjects with underlying hypertension are particularly susceptible to this effect.

Epidemiology. 2003 Sep;14(5):521-7

The protective role of antioxidants in the defence against ROS/RNS-mediated environmental pollution.

Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants, such as ionising and nonionising radiation, ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and furans, polycyclic aromatic hydrocarbons, and many other compounds present in the environment. It appears that increased oxidative/nitrosative stress is often neglected mechanism by which environmental pollutants affect human health. Oxidation of and oxidative damage to cellular components and biomolecules have been suggested to be involved in the aetiology of several chronic diseases, including cancer, cardiovascular disease, cataracts, age-related macular degeneration, and aging. Several studies have demonstrated that the human body can alleviate oxidative stress using exogenous antioxidants. However, not all dietary antioxidant supplements display protective effects, for example, β-carotene for lung cancer prevention in smokers or tocopherols for photooxidative stress. In this review, we explore the increases in oxidative stress caused by exposure to environmental pollutants and the protective effects of antioxidants.

Oxid Med Cell Longev. 2014;2014:671539

Inflammatory markers and particulate air pollution: characterizing the pathway to disease.

BACKGROUND: Increased concentrations of particles in air have been related to changes in inflammatory markers that in turn are hypothesized in mediating the particle effects on cardiovascular disease. The present work examined this association in an elderly cohort in the Greater Boston area and addresses the relative role of particles from different sources. METHODS: The study included 710 subjects, active members of the VA Normative Aging Study cohort with measurements of blood markers. Concentrations of particle number (PN), black carbon (BC), fine particulate matter (PM(2.5)), and sulphates were measured at a central site near the examination site. RESULTS: Positive associations were found between traffic-related particles (PN and BC) and inflammatory markers, but only suggestive associations were found with exposures to PM(2.5) and sulphates. The particle effect on the inflammatory markers was greater among subjects older than 78 years and among obese. A suggestion for a greater effect of particles on inflammatory markers among GSTM1-null subjects and non-users of statin drugs was also seen. CONCLUSIONS: The findings of the study support the hypothesis that particles can induce cardiovascular disease through inflammatory pathways, suggestive of a greater toxicity of traffic-related particles.

Int J Epidemiol. 2006 Oct;35(5):1347-54

Omega-3 fatty acid supplementation appears to attenuate particulate air pollution-induced cardiac effects and lipid changes in healthy middle-aged adults.

BACKGROUND: Air pollution exposure has been associated with adverse cardiovascular health effects. Findings of a recent epidemiological study suggested that omega-3 fatty acid (fish oil) supplementation blunted cardiac responses to air pollution exposure. OBJECTIVES: We conducted a randomized, controlled exposure study to evaluate the efficacy of fish oil supplements in attenuating adverse cardiac effects of exposure to concentrated ambient fine and ultrafine particulate matter (CAP). METHODS: Twenty-nine healthy middle-aged participants (mean, 58 ± 1 years of age) were supplemented in a randomized, double-blinded manner with 3 g/day of either fish oil or olive oil for 4 weeks before sequential chamber exposure to filtered air and CAP (mean mass concentration 278 ± 19 µg/m3) for 2 hr. Cardiac responses were assessed by comparing time and frequency domain changes in heart rate variability (HRV) and electrocardiographic repolarization changes measured before, immediately after, and 20 hr after exposure. Changes in plasma lipids were also evaluated at these time points. RESULTS: Fish oil supplementation appeared to attenuate CAP-induced reductions in high-frequency/low-frequency ratio, as well as elevations in normalized low-frequency HRV and prolongation of the QT interval corrected for heart rate (QTc). Very low-density lipoprotein and triglyceride concentrations increased significantly immediately after exposure to CAP in participants supplemented with olive oil, but not in those supplemented with fish oil. CONCLUSIONS: Exposure of healthy middle-aged adults to CAP for 2 hr induced acute cardiac and lipid changes after supplementation with olive oil, but not fish oil. Our findings suggest that omega-3 fatty acid supplements offer protection against the adverse cardiac and lipid effects associated with air pollution exposure.

Environ Health Perspect. 2012 Jul;120(7):952-7

Effects of watercress consumption on metabolism of a tobacco-specific lung carcinogen in smokers.

Epidemiological studies indicate that vegetable consumption protects against lung cancer in humans, but the protective constituents have not been identified. Phenethyl isothiocyanate (PEITC), which is release upon chewing of watercress (nasturtium officinale), is a chemopreventive agent against lung cancer induced by the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl-1-butanone (NNK) in rats and mice. PEITC inhibits the carcinogenicity of NNK by inhibiting its metabolic activation and thereby increasing the levels of detoxified metabolites excreted in urine. In this study, our goal was to determine whether watercress consumption would modify NNK metabolism in smokers. Eleven smokers maintained constant smoking habits and avoided cruciferous vegetables and other sources of isothiocyanates throughout the study. They donated 24-h urine samples on 3 consecutive days (baseline period). One to 3 days later, they consumed 2 ounces (56.8 g) of watercress at each meal for 3 days and donated 24-h urine samples on each of these days (watercress consumption period). One and 2 weeks later, they again donated 24-h urine samples on 2-3 consecutive days (follow-up periods). The samples were analyzed for two metabolites of NNK; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and [4-methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-omega-D-glucosiduro nic acid (NNAL- Gluc). NNAL-Gluc is believed to be a detoxification product of NNK. The urine samples were also analyzed for PEITC-NAC, a metabolite of PEITC. Minimum exposure to PEITC during the watercress consumption period averaged 19-38 mg/day. Seven of the 11 subjects had increased levels of urinary NNAL plus NNAL-Gluc on days 2 and 3 of the watercress consumption period, compared to the baseline period. Overall, the increase in urinary NNAL plus NNAL-Gluc in this period was significant [mean +/- SD 0.924 +/- 1.12 nmol/24 h (33.5%); P < 0.01]. Urinary levels of NNAl plus NNAL-Gluc returned to near baseline levels in the follow-up periods. The percentage of increase in urinary NNAL plus NNAL-Gluc during days 2 and 3 of the watercress consumption period correlated with intake of PEITC during this period, as measured by total urinary PEITC-NAC (r = 0.62; P = 0.04). The results of this study support our hypothesis that PEITC inhibits this oxidative metabolism of NNK in humans, as seen in rodents, and support further development of PEITC as a chemopreventive agent against lung cancer. This is the first study to report an effect of vegetable consumption on metabolism of a lung carcinogen in humans.

Cancer Epidemiol Biomarkers Prev. 1995 Dec;4(8):877-84.

Skin damage

Screening for Skin Cancer: US Preventive Services Task Force Recommendation Statement.

IMPORTANCE: Basal and squamous cell carcinoma are the most common types of cancer in the United States and represent the vast majority of all cases of skin cancer; however, they rarely result in death or substantial morbidity, whereas melanoma skin cancer has notably higher mortality rates. In 2016, an estimated 76,400 US men and women will develop melanoma and 10,100 will die from the disease .OBJECTIVE: To update the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for skin cancer. EVIDENCE REVIEW: The USPSTF reviewed the evidence on the effectiveness of screening for skin cancer with a clinical visual skin examination in reducing skin cancer morbidity and mortality and death from any cause; its potential harms, including any harms resulting from associated diagnostic follow-up; its test characteristics when performed by a primary care clinician vs a dermatologist; and whether its use leads to earlier detection of skin cancer compared with usual care. FINDINGS: Evidence to assess the net benefit of screening for skin cancer with a clinical visual skin examination is limited. Direct evidence on the effectiveness of screening in reducing melanoma morbidity and mortality is limited to a single fair-quality ecologic study with important methodological limitations. Information on harms is similarly sparse. The potential for harm clearly exists, including a high rate of unnecessary biopsies, possibly resulting in cosmetic or, more rarely, functional adverse effects, and the risk of overdiagnosis and overtreatment. CONCLUSIONS AND RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults (I statement).

JAMA. 2016 Jul 26;316(4):429-35

Screening program reduced melanoma mortality at the Lawrence Livermore National Laboratory, 1984 to 1996.

BACKGROUND: Worldwide incidence of cutaneous malignant melanoma has increased substantially, and no screening program has yet shown reduction in mortality. We evaluated results of an educational campaign designed to promote self-examination and targeted screening at the Lawrence Livermore National Laboratory (LLNL). METHODS: Thickness and crude incidence of melanomas detected during 3 phases of increasing melanoma surveillance were studied. These periods were: (1) preawareness (1969-1975), (2) early awareness of increased melanoma risk (1976-1984); and (3) screening program (1984-1996). Melanoma mortality was derived from data recorded in the National Death Index search. The expected annual number of deaths from melanoma among LLNL employees was calculated by using California mortality data matched by age, sex, and race/ethnicity and adjusted to exclude deaths from melanoma diagnosed before the program began or before employment at LLNL. RESULTS: Crude incidence of melanomas thicker than 0.75 mm decreased during the 3 periods from 22.1 to 15.13 to 4.62 cases per 100,000 person-years (P = .001 by chi-square for trend) with the larger decrease from the active screening program. The crude incidence of melanoma measuring less than 0.75 mm in thickness increased and then decreased slightly without a significant linear trend, and crude incidence of in situ melanoma increased substantially. No eligible melanoma deaths occurred among LLNL employees during the screening period, whereas the expected number of deaths was calculated to be 3.39 deaths (P = .034). LIMITATIONS: The study design was not randomized or controlled. The methodology for adjusting expected mortality for the exclusion of employees diagnosed with melanoma before the screening period was devised for this study.

DISCUSSION: Increasing community awareness of melanoma was associated with a progressive decreasing incidence of thicker melanoma. The education, self-examination, and selective program generated the larger reduction in incidence of melanoma thicker than 0.75 mm. This campaign decreased the melanoma-related mortality to zero. The statistically significant decrease in mortality persisted for at least 3 years after employees retired or otherwise left the laboratory.

J Am Acad Dermatol. 2008 May;58(5):741-9

Patterns of detection in patients with cutaneous melanoma.

BACKGROUND: Despite the importance of early detection in preventing mortality from melanoma, little is known regarding how patients with the disease come to diagnosis. METHODS: The authors prospectively evaluated 471 newly diagnosed melanoma patients between 1995 and 1998. Patients completed a questionnaire that included 1) identification of the person who detected the lesion, 2) the anatomic location of the lesion, and 3) family history of melanoma. Logistic regression analysis was performed to examine the relation between detection patterns and lesion thickness, adjusting for age, gender, anatomic site of the primary lesion, and family history of melanoma. RESULTS: The majority of patients detected their own melanoma (n = 270; 57%). Females were more likely to self-detect than males (69% vs. 47%; P < 0.0001). Physicians detected the melanoma in 16% of patients (n = 74), followed by "spouse" in 11% of patients (n = 51). Within this group, detection by wives was 7.5 times more common than detection by husbands (P < 0.0001). Logistic regression analysis revealed that physicians were 3.6 times more likely to detect thin lesions (</=0.75 mm) compared with nonphysician detectors (95% confidence interval [95% CI], 2.1, 6.5; P = 0.0001). In addition, patients who reported a family history of melanoma had a 2.7-fold increased likelihood of presenting with a thin lesion (95% CI, 1.6, 4.7; P = 0.0003). CONCLUSIONS: Physician detection and a report of a family history of melanoma are associated with the presentation of patients with early melanoma, suggesting that awareness of the disease among physicians and the public is critical for preventing mortality from melanoma. Increasing melanoma awareness in males may be a particularly effective means of secondary prevention.

Cancer. 2000 Jul 15;89(2):342-7

Clinical whole-body skin examination reduces the incidence of thick melanomas.

Survival from melanoma is strongly related to tumour thickness, thus earlier diagnosis has the potential to reduce mortality from this disease. However, in the absence of conclusive evidence that clinical skin examination reduces mortality, evidence-based assessments do not recommend population screening. We aimed to assess whether clinical whole-body skin examination is associated with a reduced incidence of thick melanoma and also whether screening is associated with an increased incidence of thin lesions (possible overdiagnosis). We conducted a population-based case-control study of all Queensland residents aged 20-75 years with a histologically confirmed first primary invasive cutaneous melanoma diagnosed between January 2000 and December 2003. Telephone interviews were completed by 3,762 eligible cases (78.0%) and 3,824 eligible controls (50.4%). Whole-body clinical skin examination in the three years before diagnosis was associated with a 14% lower risk of being diagnosed with a thick melanoma (>0.75 mm) (OR = 0.86, 95% CI = 0.75, 0.98). Risk decreased for melanomas of increasing thickness: the risk of being diagnosed with a melanoma 0.76-1.49 mm was reduced by 7% (OR = 0.93, 95% CI 0.79, 1.10), by 17% for melanomas 1.50-2.99 mm (OR = 0.83, 95% CI = 0.65, 1.05) and by 40% for melanomas > or =3 mm (OR = 0.60, 95% CI = 0.43, 0.83). Screening was associated with a 38% higher risk of being diagnosed with a thin invasive melanoma (< or =0.75 mm) (OR = 1.38, 95% CI = 1.22, 1.56). This is the strongest evidence to date that whole-body clinical skin examination reduces the incidence of thick melanoma. Because survival from melanoma is strongly related to tumour thickness, these results suggest that screening would reduce melanoma mortality.

Int J Cancer. 2010 Jan 15;126(2):450-8

Dermatologist detection and skin self-examination are associated with thinner melanomas: results from a survey of the Italian Multidisciplinary Group on Melanoma.

OBJECTIVE: To investigate patterns of detection and variables associated with early diagnosis of melanoma in a population at intermediate melanoma risk. DESIGN: Survey. SETTING: Hospital and university centers belonging to the Italian Multidisciplinary Group on Melanoma. PATIENTS: Eight hundred sixteen patients who were consecutively diagnosed as having melanoma and treated at 11 participating centers. MAIN OUTCOME MEASURE: Relationship between patterns of detection and patient's and physician's delay with melanoma thickness, assessed by multivariate analysis. RESULTS: A statistically significant association with early diagnosis was found for female sex (odds ratio [OR] for a lesion >1 mm in thickness, 0.70; 95% confidence interval [CI], 0.50-0.97), higher educational level (OR, 0.44; 95% CI, 0.24-0.79), residence in northern and central Italy (compared with southern Italy) (OR, 0.44; 95% CI, 0.30-0.65 and OR, 0.24; 95% CI, 0.15-0.37, respectively), and the habit of performing a skin self-examination (OR, 0.65; 95% CI, 0.45-0.93). When adjusted for all the previously mentioned variables, only melanoma detection made by a dermatologist, maybe incidentally, was associated with a statistically significant additional effect on early diagnosis (OR, 0.45; 95% CI, 0.28-0.73). No significant effect of anatomical site (trunk compared with other sites: OR, 0.83; 95% CI, 0.59-1.17), presence of atypical nevi (OR, 0.78; 95% CI, 0.52-1.17), and patient's delay (>3 months compared with < or =3 months: OR, 1.12; 95% CI, 0.78-1.60) was found. CONCLUSION: Future melanoma early diagnosis strategies should adequately stress the role of skin self-examination among the adult population, and should recommend that dermatologists perform a total skin examination to identify suspect lesions (such an examination should also be performed during consultations for other reasons).

Arch Dermatol. 2003 May;139(5):607-12

Self-detected cutaneous melanomas in Italian patients.

Self-detection of suspicious pigmented skin lesion combined with rapid referral to dermatologic centres is the key strategy in the fight against melanoma. The investigation of factors associated with pattern of detection of melanoma (self- vs. nonself-detection) may be useful to refine educational strategies for the future. We investigated the frequency of melanoma self-detection in a Mediterranean population at intermediate melanoma risk. A multicentric survey identified 816 consecutive cases of cutaneous melanoma in the period January to December 2001 in 11 Italian clinical centres belonging to the Italian Multidisciplinary Group on Melanoma. All patients filled a standardized questionnaire and were clinically examined by expert dermatologists. Self-detected melanomas were 40.6%, while the remaining lesions were detected by a dermatologist (18.5%), the family physician (15.2%), other specialists (5%), the spouse (12.5%), a friend or someone else (8.2%). Variables associated with self-detected melanomas were female sex, young age, absence of atypical nevi, knowledge of the ABCD rule, habit of performing skin self-examination. Self-detected melanomas did not differ from nonself-detected tumours in term of lesion thickness; however, patients with self-detected melanomas waited a longer period before having a diagnostic confirmation (patient's delay) (> 3 months: odds ratio, 3.89; 95% confidence interval, 2.74-5.53). In order to reduce the patients' delays, educational messages should adequately stress the need for a prompt referral to a physician once a suspicious pigmented lesion is self-detected.

Clin Exp Dermatol. 2004 Nov;29(6):593-6

Is physician detection associated with thinner melanomas?

CONTEXT: In cutaneous melanoma, tumor depth remains the best biologic predictor of patient survival. Detection of prognostically favorable lesions may be associated with improved survival in patients with melanoma. OBJECTIVE: To determine melanoma detection patterns and relate them to tumor thickness. DESIGN: Interview survey. SETTING AND PATIENTS: All patients with newly detected primary cutaneous melanoma at the Melanoma Center, Johns Hopkins Medical Institutions, between June 1995 and June 1997. MAIN OUTCOME MEASURE: Tumor thickness grouped according to detection source. RESULTS: Of the 102 patients (47 men, 55 women) in the study, the majority of melanomas were self-detected (55%), followed by detection by physician (24%), spouse (12%), and others (10%). Physicians were more likely to detect thinner lesions than were patients who detected their own melanomas (median thickness, 0.23 mm vs 0.9 mm; P<.001). When grouped according to thickness, 11 (46%) of 24 physician-detected melanomas were in situ, vs only 8 (14%) of 56 patient-detected melanomas. Physician detection was associated with an increase in the probability of detecting thinner (< or =0.75 mm) melanomas (relative risk, 4.2; 95% confidence interval, 1.4-11.1; P=.01). CONCLUSIONS: Thinner melanomas are more likely to have been detected by physicians. Increased awareness by all physicians may result in greater detection of early melanomas.

JAMA. 1999 Feb 17;281(7):640-3

Melanoma in middle-aged and older men: a multi-institutional survey study of factors related to tumor thickness.

OBJECTIVES: To identify factors related to the detection of melanoma and to determine those that differ between thinner vs thicker tumors in middle-aged and older men. DESIGN: Survey. SETTING: Three institutional melanoma clinics. PARTICIPANTS: Men 40 years or older who had newly diagnosed invasive melanoma. MAIN OUTCOME MEASURES: Differences in melanoma awareness, skin examination practices, discovery patterns, and social/medical care factors relative to tumor thickness. RESULTS: Two hundred twenty-seven men completed surveys within 3 months of melanoma diagnosis; 57 (25.1%) had thicker tumors (>2.00 mm). Thicker tumors were associated with nodular histologic features (43.9%), a lack of atypical nevi, having less than a high school education, and patient vs physician (dermatologist or nondermatologist) detection. Knowledge of melanoma (P = .007), attention to skin cancer detection information (P = .02), an interest in health topics (P = .003), and knowing the importance of physician skin examination (P = .05) were more common in those with thin tumors. Tumor thickness did not correlate with age, anatomic location, marital/cohabitation status, prior skin cancer, or sun sensitivity. Overall patient awareness of melanoma warning signs, skin self-examination practices, and Internet use were poor (<20%, <50%, and <14%, respectively). CONCLUSIONS: Physician discovery, the patient's higher level of education and detection-promoting awareness and attitudes, and the presence of clinically atypical nevi were related to thinner melanomas. Innovative outreach strategies and novel educational campaigns incorporating these factors, coupled with sharper messages regarding the importance of physician screening, are needed to improve early detection in middle-aged and older men.

Arch Dermatol. 2009 Apr;145(4):397-404

A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention.

BACKGROUND: Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. METHODS: In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide. RESULTS: At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001). No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued. CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. (Funded by the National Health and Medical Research Council; ONTRAC Australian New Zealand Clinical Trials Registry number, ACTRN12612000625875.).

N Engl J Med. 2015 Oct 22;373(17):1618-26

Dry eye

A randomized controlled trial of omega-3 fatty acids in dry eye syndrome.

AIM: To evaluate the role of dietary supplementation of omega-3 fatty acids in dry eye syndrome. METHODS: A prospective, interventional, placebo controlled, double blind randomized trial was done at two referral eye centers. Two hundred and sixty-four eyes of patients with dry eye were randomized to receive one capsule (500mg) two times a day containing 325mg EPA and 175mg DHA for 3 months (omega-3 group). The omega-3 group was compared to a group of patients (n=254) who received a placebo (placebo group). There were 4 patient visits (at baseline, 1 month, 2 months and 3 months). On each visit, recording of corrected distance visual acuity (CDVA), slit lamp examination and questionnaire based symptom evaluation and scoring was done. A symptomatic score of 0-6 was mild, 6.1-12 moderate and 12.1-18 severe dry eye. Response to intervention was monitored by routine tear function tests like Schirmer I test, tear film break-up time (TBUT), Rose Bengal staining and most notably, conjunctival impression cytology. RESULTS: Sixty-five percent of patients in the omega-3 group and 33% of patients in placebo group had significant improvement in symptoms at 3 months (P=0.005). There was a significant change in both Schirmer's test value and TBUT values in the omega-3 group (P<0.001), both comparisons. However, there was a larger drift in TBUT values in omega-3 than the placebo group, in comparison to Schirmer's test values. The mean TBUT score was 2.54±2.34 in the omega-3 group and 0.13±0.16 in placebo group, respectively. The mean reduction in symptom score in omega-3 group was 2.02±0.96 as compared to 0.48±0.22 in placebo group (P<0.001). Despite a slight increase mean score, the Schirmer scores did not correlate well with symptomatic improvement. CONCLUSION: Omega-3 fatty acids have a definite role for dry eye syndrome. The benefit seems to be more marked in conditions such as blepharitis and meibomian gland disease. The role of omega fatty acids in tear production and secretion needs further evaluation.

Int J Ophthalmol. 2013 Dec 18;6(6):811-6

Are higher blood mercury levels associated with dry eye symptoms in adult Koreans? A population-based cross-sectional study.

OBJECTIVES: The purpose of this study was to investigate whether blood mercury concentrations associated with the presence of dry eye symptoms in a nationally representative Korean population. METHODS: Population-based prospective cross-sectional study using the heavy metal data set of the 2010-2012 Korean National Health and Nutrition Examination Survey (KNHANES). A total of 4,761 adult Koreans were the eligible population in this study. Of the 7,162 survey participants, 2,401 were excluded because they were <19 years of age, there were missing data in the heavy metal data set, or they had diabetes, rheumatoid arthritis, thyroid disease, asthma, depression and/or under-the-eye surgery. Blood mercury levels were measured on the day the participants completed a questionnaire regarding the presence of dry eye symptoms (persistent dryness or eye irritation). The population was divided into low and high groups by median level (4.26 and 2.89 µg/L for males and females, respectively). RESULTS: Self-reported dry eye symptoms were present in 13.0% of the cohort. Participants with dry eye symptoms were significantly more likely to have blood mercury levels exceeding the median than those without dry eye symptoms (45.7% vs 51.7%, p=0.021). Logistic regression analysis showed that, after adjusting for age, gender, education, total household income, smoking status, heavy alcohol use, sleep time, perceived stress status, total cholesterol levels and atopy history, dry eye symptoms were significantly associated with blood mercury levels that exceeded the median (reference: lower mercury group; OR, 1.324; 95% CI 1.059 to 1.655; p<0.05). CONCLUSIONS: High blood mercury levels were associated with dry eye symptoms in a nationally representative Korean population.

BMJ Open. 2016 Apr 27;6(4):e010985

Pharmacological management of dry eye in the elderly patient.

Dry eye disease is a common and increasingly prevalent condition particularly associated with advancing age and postmenopausal women. Epidemiological studies identify prevalence rates ranging from 7% in the US to 33% in the Asian population. Research increasingly identifies risk factors of increasing age, female sex, smoking, use of video display terminals and use of certain medications as well as environmental stresses as aggravating factors for the disease. Basic and clinical investigations provide cumulative evidence of hyperosmolarity of the tear film and ocular surface/lacrimal gland inflammation as pathogenic features of dry eye disease. A decline in systemic and local levels of sex hormones is associated with advancing age and advancing disease. Pharmacological therapeutic interventions include enhanced lubricants and anti-inflammatory drugs such as topical corticosteroids and ciclosporin (cyclosporine A). Secretagogues and hormonal supplementation are potential future therapies. The increased understanding of the contributing and pathogenetic factors responsible for dry eye provides a rationale for multiple therapeutic options for this multi-factorial disease. In the elderly patient it is important to recognize the physical and cognitive limitations that will influence the selection of appropriate topical medication.

Drugs Aging. 2008;25(2):105-18

The role and treatment of inflammation in dry eye disease.

Dry eye syndrome is a common ocular surface problem, affects 10-30 % of the population, especially in those who are older than 40 years. As a consequence of the demographic pressure created by the aging population, its prevalence is expected to increase as well as its burden on ophthalmologic practices. Thus, understanding the complex underlying mechanisms and development of thoughtful, effective strategies that involve these mechanisms are critical. Many factors causing ocular surface damage and inflammation have been shown to contribute to the etiopathogenesis. Increased osmolarity induces ocular surface inflammation leading to disruption of both the quality and quantity of tears. Pathologic tear function and the ocular surface inflammation affects the neural arcade and increases apoptosis in the ocular surface cells thus creating a viscous cycle for dry eye by causing unstable and hyperosmolar tears. Thus, the treatment objective is to prevent severe dry eye complications via preventing inflammation and apoptosis of the ocular surface cells. The ultimate target is a normalized ocular surface, increased tear stability, and decreased osmolarity of the tear film. In the light of current literature, this review aims to elucidate the role of inflammation as the main etiological factor in dry eye disease and discuss current therapeutic approaches to overcome it.

Int Ophthalmol. 2014 Dec;34(6):1291-301

Impact of evaporation on aqueous tear loss.

PURPOSE: To determine the impact of evaporation on preocular aqueous tear (AT) loss in normal subjects (controls) and patients with keratoconjunctivitis sicca (KCS). METHODS: Eighteen patients (32 eyes) with KCS with or without associated meibomian gland dysfunction (MGD) and 11 sex-matched controls had AT evaporation determined between relative humidity (RH) of 20% and 45% using an evaporometer. AT volume, flow, and turnover were determined with a fluorophotometer. RESULTS: Evaporative rates increased significantly when the RH was changed from 40%-45% to 20%-25% (P < .001). This change was similar in all groups and on average accounted for a 99.43% increase. There were no statistically significant differences in evaporative rate between controls, the KCS alone group, and the KCS/MGD group. Dry eye patients exhibited a decreased tear turnover when compared to controls. Evaporative contribution to tear loss at 40%-45% RH was 23.47% for controls, 30.99% for "classic" KCS patients, and 25.44% for KCS/MGD patients. At 20%-25% RH, the evaporative contribution was 41.66% for controls, 57.67% for classic KCS patients, and 50.28% for KCS/MGD patients. CONCLUSIONS: RH significantly impacts evaporation regardless of the presence of dry eye disease and probably accounts for the increased dry eye symptoms in people (controls and dry eye patients) in conditions of low RH (eg, deserts, airplane cabins, cold dry seasons). Contribution of evaporation to tear loss tends to be higher than previously described. The percent contribution is dependent on environmental conditions such as RH. There was a trend toward increased contribution to AT loss in dry eye patients vs controls, but statistical significance was not reached.

Trans Am Ophthalmol Soc. 2006;104:121-8

Etiology, prevalence, and treatment of dry eye disease.

PURPOSE: This review article examines the prevalence, etiology, and current therapies of dry eye disease, with special focus on postmenopausal women. METHOD: A systematic literature search utilizing MEDLINE was conducted to identify peer-reviewed articles related to dry eye published prior to September 2008. The terms "dry eye" and "women" were searched in combination with one or more of the following words or phrases: prevalence, postmenopausal, etiology, risk factors, therapy, medications, surgery, tear film, and quality of life. Articles were selected based on their direct applicability to the subject matter. A manual search was also conducted based on citations in the published literature. RESULTS: Epidemiologic studies identified prevalence rates ranging from 7% in the United States to 33% in Taiwan and Japan. Risk factors include advanced age, female sex, smoking, extreme heat or cold weather conditions, low relative humidity, use of video display terminals, refractive surgery, contact lens wear, and certain medications. CONCLUSION: The last decade has brought about a better understanding of the etiology of dry eye disease. New therapies that can alleviate the signs and symptoms of dry eye disease and, consequently, improve the quality of life of dry eye patients are available in the market.

Clin Ophthalmol. 2009;3:405-12

The impact of artificial tears containing hydroxypropyl guar on mucous layer.

PURPOSE: The aim of this study was to investigate the effect of lubricant eyedrops containing propylene glycol 400 (PEG) and polyethylene glycol (PG) with hydroxypropyl guar (HP-guar) as a gelling agent on the precorneal mucous layer in vivo. METHODS: Sixteen New Zealand white rabbits were randomly assigned to 1 of 4 groups. All rabbits received PEG/PG/HP-guar tear products in the right eye. PEG/PG/HP-guar with Polyquad, 0.1% hyaluronate sodium, 0.5% carboxymethylcellulose, or phosphate-buffered saline was placed in the left eyes of animals in each group. All eyedrops were used 4 times a day for 7 days. An additional 8 rabbits were randomly assigned to 1 of 2 groups. One group received PEG/PG/HP-guar products 4 times a day for 7 days (long-term exposure group), and the other group received PEG/PG/HP-guar products 3 times at 5-minute intervals (short-term exposure group). Fifteen minutes after the last drop was administered, each cornea was immediately excised and mucous layer thickness measured by transmission electron microscopy. RESULTS: Mucous layer thickness was significantly greater in eyes treated with PEG/PG/HP-guar products compared with those treated with 0.1% hyaluronate sodium, 0.5% carboxymethylcellulose, or phosphate-buffered saline (all P values < 0.001). There were no significant differences in mucous layer thickness between PEG/PG/HP-guar products and PEG/PG/HP-guar with Polyquad or in the long- and short-term exposure animals. CONCLUSIONS: This study demonstrates that even a short exposure to PEG/PG/HP-guar tear product increased precorneal mucous layer thickness.

Cornea. 2010 Dec;29(12):1430-5