Below What FEV1 Should Arterial Blood be Routinely Taken to Detect Chronic Respiratory Failure in COPD?

IntroductionTo diagnose and assess chronic respiratory failure in stable chronic obstructive pulmonary disease (COPD) the measurement of arterial blood gases (ABG) is required. It has been suggested that ABG could be determined for this purpose when FEV₁ ranges between 50% and 30% predicted, but these thresholds are not evidence-based.ObjectiveTo identify the post-bronchodilator (BD) FEV₁ and arterial oxygen saturation (SaO₂) values that provide the best sensitivity, specificity, and likelihood ratio (LR) for the diagnosis of hypoxaemic and/or hypercapnic chronic respiratory failures in stable COPD.MethodsA total of 150 patients were included (39 with PaO₂ < 60 mm Hg [8 kPa], 14 of them with a PaCO₂ ≥ 50 mm Hg [6.7 kPa]). The best post-BD FEV₁ and SaO₂ cut-off points to predict chronic respiratory failure were selected using the PC and the Receiver Operating Characteristics (ROC) curves.ResultsA post-BD FEV₁ equal to 36% and an SaO₂ of 90% were the best predictive values for hypoxaemic respiratory failure and a post-BD FEV₁ equal to 33% for the hypercapnic variant. An FEV₁ ≥ 45% ruled out hypoxaemic respiratory failure.ConclusionA post-BD FEV₁ of 36% is the best cut-off point to adequately predict both hypoxaemic and hypercapnic respiratory failure in the patient with stable COPD. For its part, an SaO₂ of 90% is the best value for isolated hypoxaemic failure. These values could be considered for future clinical recommendations/guidelines for COPD.     

Validation of the Danish version of the revised cystic fibrosis quality of life questionnaire in adolescents and adults (CFQ-R14+)

BackgroundQuality of life is an important parameter in the evaluation of quality and outcome of health care and treatment, especially in patients with chronic disorders. The aim of this study was to assess the validity and reliability of the Danish version of the revised disease-specific health-related quality of life questionnaire for adolescents and adults with cystic fibrosis (CFQ-R14+).MethodsA total of 196 cystic fibrosis (CF) patients completed the CFQ-R14+ (response rate 71%). Forced expiratory volume in 1 s in percentage of predicted (FEV₁%) and body mass index (BMI) were included as measures of health status.ResultsInternal consistency coefficients ranged from 0.54 to 0.95. Eight out of the twelve scales had alpha coefficients above 0.7. Test–retest correlations ranged from 0.42 to 0.88 and they were significant in eight scales. All the CFQ-R+14 scales except the digestive symptoms scale discriminated significantly (p < 0.05) between patients with mild, moderate, and severe disease. Nine out of the twelve scales discriminated significantly (p < 0.05) between nourished (BMI ≥ 19) and malnourished (BMI < 19) patients. Significant differences between participants and non-responders were found for age, sex and FEV₁ (higher age, more males and lower FEV₁ among non-responders). All of the scales met standards for floor effects (< 15% of the responders with the lowest score) but five of the scales failed to meet standards for ceiling effects (> 15% of the responders with the highest score).ConclusionThe Danish CFQ-R14+ is a reliable and valid instrument for measuring the health-related quality of life in Danish adolescents and adults with CF, though with the exception from a few of its subscales.     

Risk factors for rate of decline in FEV(1) in adults with cystic fibrosis

BackgroundPreviously we assessed risk factors for FEV₁ decline in children and adolescents using the Epidemiologic Study of Cystic Fibrosis (J Pediatr 2007;151:134–139); the current study assessed risk factors in adults.MethodsRisk factors for FEV₁ decline over 3–5.5 years for ages 18–24 and ≥ 25 years were assessed using mixed-model regression.ResultsMean rates of FEV₁ decline (% predicted/year) were − 1.92 for ages 18-24y (n = 2793) and − 1.45 for ages ≥ 25y (n = 1368). For the 18-24y group, B. cepacia, pancreatic enzyme use, multidrug-resistant P. aeruginosa, cough, mucoid P. aeruginosa, and female sex predicted greater decline; low baseline FEV₁ and sinusitis predicted less decline. For the ≥ 25y group, only pancreatic enzyme use predicted greater decline; low baseline FEV₁ and sinusitis predicted less decline.ConclusionsRisk factors for FEV₁ decline in adults < 25 years are similar to those previously identified in children and adolescents; older adults had few statistically significant risk factors.     

Ancestral haplotype 8.1 and lung disease severity in European cystic fibrosis patients

BackgroundThe clinical course of cystic fibrosis (CF) lung disease varies between patients bearing identical CFTR mutations. This suggests that additional genetic modifiers may contribute to the pulmonary phenotype. The highly conserved ancestral haplotype 8.1 (8.1AH), carried by up to one quarter of Caucasians, comprises linked gene polymorphisms on chromosome 6 that play a key role in the inflammatory response: LTA + 252A/G; TNF −308G/A, HSP70-2 + 1267A/G and RAGE −429T/C. As inflammation is a key component inducing CF lung damage, we investigated whether the 8.1AH represents a lung function modifier in CF.MethodsWe analyzed the lung function of 404 European CF patients from France (n = 230), Germany (n = 95) and UK (n = 79). FEV₁ differences between 8.1AH carriers and non-carriers were calculated in each country and pooled using a random effects model.ResultsThe frequency of 8.1AH carriers was similar between French (22%), German (29%) and UK (27%) patients. We found that 8.1AH carriers had significantly lower FEV₁, adjusted for age classes and countries (P < 0.04, mean FEV₁ difference − 6.4% CI95% [− 12.4%, − 0.5%]). No difference was observed with respect to BMI Z-scores and chronic colonization with P. aeruginosa.ConclusionsThese findings support the concept that 8.1AH is an important genetic modifier of lung disease in CF. To conclude, multiple linked genes outside the CF locus might explain some of the variability in lung phenotype.     

Multiple antibiotic-resistant Pseudomonas aeruginosa and lung function decline in patients with cystic fibrosis

BackgroundThe goal of this study was to determine the association of multiple antibiotic-resistant Pseudomonas aeruginosa (MARPA) acquisition with lung function decline in patients with cystic fibrosis (CF).MethodsUsing data from Epidemiologic Study of Cystic Fibrosis (ESCF), we identified patients with spirometry data and MARPA, defined as PA (1) resistant to gentamicin and either tobramycin or amikacin, and (2) resistant to ≥ 1 antipseudomonal beta lactam. MARPA had to be detected in a respiratory culture after ≥ 2 years of PA-positive but MARPA-negative respiratory cultures. Multivariable piecewise linear regression was performed to model the annual rate of decline in forced expiratory volume in 1 second (FEV₁) % predicted 2 calendar years before and after the index year of MARPA detection, adjusting for patient characteristics and CF therapies.ResultsIn total, 4349 patients with chronic PA and adequate PFT data were identified; 1111 subsequently developed MARPA, while 3238 patients were PA positive but MARPA negative. Compared with patients who did not acquire MARPA, MARPA-positive patients had lower FEV₁ and received more oral (p < 0.013) and inhaled (p < 0.001) antibiotic therapy. Mean FEV₁ decline did not change significantly after MARPA detection (− 2.22% predicted/year before detection and − 2.43 after, p = 0.45). There was no relationship between persistent infection or FEV₁ quartile and FEV₁ decline.ConclusionsNewly detected MARPA was not associated with a significant change in the rate of FEV₁ decline. These results suggest that MARPA is more likely to be a marker of more severe disease and more intensive therapy, and less likely to be contributing independently to more rapid lung function decline.     

Temocillin in cystic fibrosis: A retrospective pilot study

BackgroundTemocillin is currently used in the treatment of acute pulmonary exacerbations caused by Burkholderia cepacia complex and multi-resistant Pseudomonas aeruginosa in cystic fibrosis (CF) patients despite little published clinical data. This study assessed if intravenous (IV) antibiotic therapy including temocillin was equivalent to standard combination therapy for an acute exacerbation.MethodsA retrospective, pilot cross-over study. Adult patients attending two CF centres between 1997 and 2006 who had received a course of IV antibiotics including temocillin (TIV) and a further IV course (within ± 1 year) which did not include temocillin (NTIV) were included. Outcome measures at the start and end of each IV course were recorded (FEV₁%, FVC%).ResultsTwenty six patients had received temocillin. Baseline values of FEV₁% predicted were comparable for both groups (TIV: 37(18%), NTIV: 39(20%)). FEV₁% increased by 7.12(11.67)% after TIV (p < 0.01) and 6.65(7.62)% after NTIV (p < 0.01). There was no significant difference between the IV courses in mean %change in lung function TIV versus NTIV (FEV₁ 0.46% [95%CI: − 4.55 to 5.48%]).ConclusionThese data suggest equivalence in the lung function outcome of IV antibiotic therapy includingtemocillin versus standard IV antibiotic therapy.     

A randomized placebo-controlled trial of miglustat in cystic fibrosis based on nasal potential difference

BackgroundPreclinical data suggest that miglustat could restore the function of the cystic fibrosis transmembrane conductance regulator gene in cystic fibrosis cells.MethodsSingle-center, randomized, double-blind, placebo-controlled, crossover Phase II study in 11 patients (mean ± SD age, 26.3 ± 7.7 years) homozygous for the F508del mutation received oral miglustat 200 mg t.i.d. or placebo for two 8-day cycles separated by a 14-day washout period. The primary endpoint was the change in total chloride secretion (TCS) assessed by nasal potential difference.ResultsNo statistically significant changes in TCS, sweat chloride values or FEV₁ were detected. Pharmacokinetic and safety were similar to those observed in patients with other diseases exposed to miglustat.ConclusionsThere was no evidence of a treatment effect on any nasal potential difference variable. Further studies with miglustat need to adequately address criteria for assessment of nasal potential difference.     

Prevalence and impact on FEV(1) decline of chronic methicillin-resistant Staphylococcus aureus (MRSA) colonization in patients with cystic fibrosis. A single-center, case control study of 165 patients

BackgroundRisk factors for methicillin-resistant Staphylococcus aureus (MRSA) in Cystic Fibrosis (CF) and the impact on CF disease progression are still under debate.The objectives of this study were to determine clinical variables associated with MRSA colonization and examine impact on FEV₁ evolution in CF patients.MethodsA retrospective case–control study using the University Hospital of Brussels CF clinic patient registry from 2002 to 2010, comparing clinical variables and decline of FEV₁ of MRSA positive patients with age and sex matched controls, chronically colonized with S. aureus.ResultsThirty of the 165 CF patients, chronically colonized with S. aureus, had cultures positive for MRSA (18.2%). Excluding patients under 4 years, the prevalence became 15.2% (23/151). Chronic colonization (i.e., three or more consecutive positive cultures) was found in 19/151 (12.6%).The MRSA positive group showed a higher proportion of patients with genotype F508del, less pancreas sufficient patients, more bronchiectasis and more frequent hospitalization.The FEV₁ recorded one year prior to, and at the moment of MRSA acquisition, was lower but not significantly different from that obtained in controls (72.9% ± 26.6 vs 84.3 ± 21.8 and 68.2% ± 27.1 vs 81.4% ± 24.3 respectively, p > 0.1). However, FEV₁ decline over 2- and 6-year periods, were significantly greater in the chronic MRSA group than in the controls (− 5% ± 5.5 vs −2.5 ± 2.3 over 2 years (p = 0.043) and − 1.8% ± 4.6 vs −1.0% ± 1.9 over a 6-year period (p = 0.026)).ConclusionIn our center the prevalence of MRSA in CF patients, chronically colonized with S. aureus and over the age of 4 years, was 15.2% (12.6% chronic infection). MRSA colonization was shown to be associated with a genotype F508del, presence of bronchiectasis and hospitalization. Our spirometric data also show that a MRSA episode entails an FEV₁ decline that is almost double that predicted for CF patients who can remain unaffected by MRSA.     

Prevalence of Chronic Obstructive Pulmonary Disease in the Canary Islands

IntroductionThe prevalence of chronic obstructive pulmonary disease (COPD) varies significantly among the different geographical areas reported. In Spain, two epidemiological studies have shown a prevalence of 9–10% in the population aged over 40. However, neither of these studies included the Canary Islands, which are of interest due to their climatic conditions and high incidence of smoking.Materials and methodsA random group of 1353 subjects aged between 40 and 70 years was selected from a sample population of 596 478 individuals. Participants completed a questionnaire and then performed spirometry with bronchodilator testing if obstruction was observed. COPD was diagnosed when the post-bronchodilator FEV₁/FVC ratio was less than 0.70.ResultsThe prevalence of COPD was 7.3% (95%CI: 5.5–9.5) and was higher in males than in females (8.7% vs 6.3%, P=.134). The incidence of smoking was 29.4% (95%CI: 25.4–33.1) and was also higher in males than in females (35.1% vs 25.4%, P<.001). The prevalence of COPD stratified by severity of obstruction, according to the GOLD criteria, was 16% in group I, 69.9% in group II, 10.4% in group III and 3.3% in group IV. 71.6% of the subjects were underdiagnosed and 63.5% undertreated.ConclusionsDespite having one of the highest rates of smoking in Spain, the prevalence of COPD in the Canary Islands is lower than in most of the Spanish regions studied.     

The impact of osteoporosis and vertebral compression fractures on mortality and association with pulmonary function in COPD: A meta-analysis

ObjectiveOsteoporosis is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and most commonly presents as a vertebral compression fracture (VCF). Our objective was to quantify the effect of osteoporosis and VCFs on the mortality and pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC), of patients with COPD.MethodsA PubMed/Medline search was conducted using the search terms “chronic obstructive pulmonary disease”, “osteoporosis” and “vertebral compression fracture”. Meta-analyses were conducted to evaluate the differences in mortality and PFTs between patients with COPD with and without osteoporosis or VCFs, according to PRISMA guidelines. PROSPERO registration: CRD42019120335.ResultsOf the 896 abstracts identified, 27 studies describing 7662 patients with COPD of which 1883 (24.6%) had osteoporosis or VCFs, were included. Random effects model analysis demonstrated that patients with COPD and osteoporosis or VCFs had an increased OR for mortality of 2.40 (95% CI: 1.24; 4.64, I² = 89%, P < 0.01), decreased FEV₁/FVC with a mean difference of ?4.80% (95% CI: ?6.69; ?2.90, I² = 83%, P < 0.01) and decreased FEV₁, with a mean difference of ?4.91% (95% CI: ?6.51; ?3.31, I² = 95%, P < 0.01) and ?0.41 L (95% CI: ?0.59; ?0.24, I² = 97%, P < 0.01), compared to control subjects. Apart from FEV₁ (liters) in subgroup 1 (P = 0.06), all subgroup analyses found significant differences between groups, as did sensitivity analysis of low risk of bias studies.ConclusionOsteoporosis and VCFs are associated with a significant reduction in survival and pulmonary function among patients with COPD.     

Long-term non-invasive ventilation in cystic fibrosis -- experience over two decades

BackgroundNon-invasive ventilation (NIV) is accepted as a bridge to lung transplantation in cystic fibrosis (CF) but there is little evidence to support its use outside this setting.MethodsWe reviewed the records of all patients with CF who received domiciliary NIV at our centre between 1991 and 2010.ResultsOf 47 patients studied, 36% underwent lung transplantation, 28% died without transplantation and 30% remain alive on NIV. Median duration of NIV was 16 months (range 2–90). Mean FEV₁ fell by 212 ml over the year before NIV but increased by 18 ml in the following year (p < 0.01). Individual response to NIV was associated with lower baseline and more rapid decline in FEV₁. From 1991 to 2000, 70% underwent lung transplantation; from 2001 to 2010 only 27% were transplanted.ConclusionsNIV may slow or reverse the decline in lung function in advanced CF. NIV is increasingly used beyond a bridge to transplantation at our centre.     

Psoas Muscle Density Evaluated by Chest CT and Long-Term Mortality in COPD Patients

RationalePoor muscle quality in COPD patients relates to exercise intolerance and mortality. Muscle quality can be estimated on computed tomography (CT) by estimating psoas density (PsD). We tested the hypothesis that PsD is lower in COPD patients than in controls and relates to all-cause mortality.MethodsAt baseline, PsD was measured using axial low-dose chest CT images in 220 COPD patients, 80% men, who were 65 ± 8 years old with mild to severe airflow limitation and in a control group of 58 subjects matched by age, sex, body mass index (BMI) and body surface area (BSA). COPD patients were prospectively followed for 76.5 (48–119) months. Anthropometrics, smoking history, BMI, dyspnoea, lung function, exercise capacity, BODE index and exacerbations history were recorded. Cox proportional risk analysis determined the factors more strongly associated with long-term mortality.ResultsPsD was lower in COPD patients than in controls (40.5 vs 42.5, p = 0.045). During the follow-up, 54 (24.5%) deaths occurred in the COPD group. PsD as well as age, sex, pack-year history, FEV₁%, 6MWD, mMRC, BODE index, were independently associated with mortality. Multivariate analysis showed that age (HR 1.06; 95% CI 1.02–1.12, p = 0.006) and CT-assessed PsD (HR 0.97; 95%CI 0.94–0.99, p = 0.023) were the variables independently associated with all-cause mortality.ConclusionsIn COPD patients with mild to severe airflow limitation, chest CT-assessed psoas muscle density was lower than in matched controls and independently associated with long-term mortality. Muscle quality using the easy to evaluate psoas muscle density from chest CT may provide clinicians with important prognostic information in COPD.     

HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population

IntroductionWhile the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry.MethodsCOPD patients (n = 214) and age-matched controls (n = 193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers.ResultsCODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p = 0.04, OR = 2.07). HLA-DRB1*01:02 was also significantly associated with FEV₁ (p = 0.04) and oxygen saturation (p = 0.02), and the FEV₁/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p = 9 × 10^?3).ConclusionWe report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.     

Clinical evidence that V456A is a Cystic Fibrosis causing mutation in South Asians

BackgroundCystic Fibrosis (CF) genotypes in South Asians are variable with a decreased incidence of Delta F508 and an increased incidence of novel mutations. The objective of this study is to provide clinical evidence that V456A, a novel mutation in South Asian Cystic Fibrosis patients, can cause significant lung disease.MethodsWe extracted clinical data from a retrospective chart review of 2 CF patients of South Asian descent.ResultsPatient 1, a 10 year and 11 month old Pakistani female at her initial clinic visit, required multiple hospitalizations for bronchiectasis and pulmonary infections. She was pancreatic sufficient but had slow weight gain. Genetic testing revealed that she is homozygous for the CFTR V456A mutation. Patient 2, an Indian female diagnosed with CF on newborn screening, is compound heterozygous for V456A/R709X. She had slow weight gain with BMI ranging from 12.9 to 13.4 kg/m² from 3 to 5 years of age and was 14.2 kg/m² at 6 years of age. At 6 years of age, pulmonary function tests revealed mild lung disease with FVC of 71%, FEV₁ of 75%, FEF_25–75 of 119%, and FEV₁/FVC of 86% predicted. Sputum cultures were intermittently positive for Staphylococcus aureus and Haemophilus influenza.ConclusionsWe provide evidence that V456A can cause significant pulmonary disease in South Asian Cystic Fibrosis patients.     

Pooled analysis of two large randomised phase III inhaled mannitol studies in cystic fibrosis

BackgroundTo evaluate safety and efficacy of inhaled mannitol treatment in subgroups of a large global CF population.MethodsData were pooled from two multicentre, double-blind, randomised, controlled, parallel group phase III studies in which 600 patients inhaled either mannitol (400 mg) or control (mannitol 50 mg) twice a day for 26 weeks.ResultsBoth the mean absolute change in FEV₁ (mL) and relative change in FEV₁ by % predicted from baseline for mannitol (400 mg) versus control were statistically significant (73.42 mL, 3.56%, both p < 0.001). Increases in FEV₁ were observed irrespective of rhDNase use. Significant improvements in FEV₁ occurred in adults but not children (6–11) or adolescents (aged 12–17). Pulmonary exacerbation incidence was reduced by 29% (p = 0.039) in the mannitol (400 mg) group.ConclusionsSustained six-month improvements in lung function and decreased pulmonary exacerbation incidence indicate that inhaled mannitol is an important additional drug in the treatment of CF.     

Accuracy of a New Algorithm to Identify Asthma–COPD Overlap (ACO) Patients in a Cohort of Patients with Chronic Obstructive Airway Disease

Objectives

We aimed to characterize the clinical, functional and inflammatory features of patients diagnosed diagnosed with ACO according to a new algorithm and to compare them with those of other chronic obstructive airway disease (COAD) categories (asthma and COPD).

Inter-examiner reliability of palpation for tissue texture abnormality in the thoracic paraspinal region

BackgroundPalpation of soft tissue changes is claimed to be important for osteopathic diagnosis and treatment. Few studies, however, have examined the inter-examiner reliability for the detection of altered segmental paraspinal tissue texture.ObjectiveTo determine the inter-examiner reliability of the identification of abnormal tissue texture in the thoracic paraspinal region using palpation.MethodTen final-year osteopathic students examined the thoracic paravertebral gutter regions of ten subjects presenting with a recent history of thoracic symptoms. Each examiner palpated each subject to determine which of four predetermined areas exhibited the most obvious alteration or abnormality in tissue texture. One week prior to the study, all examiners received consensus training to standardise the method of palpation.ResultsThe inter-examiner agreement for the site with the most marked tissue texture change was fair (κ = 0.26; P_o = 0.46; P_e = 0.28; 95% CI 0.19–0.33). When only the first five assessments from each examiner were analysed, the agreement improved slightly, but remained fair (κ = 0.32; P_o = 0.52; P_e = 0.30; 95% CI 0.16–0.47).ConclusionsInter-examiner reliability of palpation for abnormal tissue texture in the deep thoracic paraspinal region was only fair. The influence of either examiner fatigue or tissue change due to repeated palpation appeared to be small. Although the practice of palpating for segmental tissue texture abnormalities without concurrent reports of tenderness from the patient is not typical of clinical practice, this study suggests that assessment of texture change is complex and not highly reproducible between examiners.     

Changes in Control Status of COPD Over Time and Their Consequences: A Prospective International Study

IntroductionControl status may be a useful tool to assess response to treatment at each clinical visit in COPD. Control status has demonstrated to have long-term predictive value for exacerbations, but there is no information about the short-term predictive value of the lack of control and changes in control status over time.MethodProspective, international, multicenter study aimed at describing the short-term (6 months) prognostic value of control status in patients with COPD. Patients with COPD were classified as controlled/uncontrolled at baseline and at 3,6-month follow-up visits using previously validated criteria of control. Moderate and severe exacerbation rates were compared between controlled and uncontrolled visits and between patients persistently controlled, uncontrolled and those changing control status over follow-up.ResultsA total of 267 patients were analyzed: 80 (29.8%) were persistently controlled, 43 (16%) persistently uncontrolled and 144 (53.7%) changed control status during follow-up. Persistently controlled patients were more frequently men, with lower (not increased) body mass index and higher FEV₁(%). During the 6 months following an uncontrolled patient visit the odds ratio (OR) for presenting a moderate exacerbation was 3.41 (95% confidence interval (CI) 2.47–4.69) and OR = 4.25 (95%CI 2.48–7.27) for hospitalization compared with a controlled patient visit.ConclusionsEvaluation of control status at each clinical visit provides relevant prognostic information about the risk of exacerbation in the next 6 months. Lack of control is a warning signal that should prompt investigation and action in order to achieve control status.     

Increased risk of cancer among gout patients: a nationwide population study

ObjectiveFew studies have investigated the association between gout and cancer. The present study examined the relative risk of cancer in a nationwide cohort.MethodsThe primary data source was the National Health Insurance database of Taiwan. Data recorded between 2000 and 2008 for subjects ≥ 20 years and with no history of malignancy were included for the analysis. A gout case definition was defined by records of gout diagnosis and anti-gout treatment (urate-lowering drugs, including allopurinol, benzbromazone, probenacid and sulfinpyrazone, and colchicine). Cox proportional hazards models were used to examine the association between gout and cancer.ResultsA total of 694,361 patients (355,278 men, 339,083 women) were included; among them, 25,943 had a history of gout. Mean age (± standard deviation) was 42.3 ± 16.3 years. During 5,471,272 patient-years of follow-up, cancer was detected in 24,088 patients (1745 with gout and 22,343 controls). The most cancers were liver, lung, and colonic cancers. The overall incidence of cancer was significantly higher among gout patients than controls (8.7 vs. 4.2 cases per 1000 patient-years, P < 0.001). After adjustment for age and sex, gout was found to be associated with a hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.10–1.21; P < 0.001) for cancer. Gout was most closely associated with prostate cancer, with an age- and sex-adjusted HR of 1.71 (1.45–2.02). On the other hand, gout tended to have an inverse, albeit insignificant, association with breast cancer (adjusted HR, 0.81; 95% CI, 0.63–1.04).ConclusionGout was associated with increased risk of cancer, particularly that of prostate cancer in males.