CRP is associated with lung function decline in men but not women: a prospective study.

Systemic inflammation is associated with impaired lung function. Studies, most cross-sectional, report a stronger association between systemic inflammation and lung function impairment in men than women. The aim was to evaluate gender differences in the longitudinal association between systemic inflammation and lung function. We used data from randomly chosen residents of Reykjavík, born 1940-54, who were investigated in three stages: Baseline (1973-75; 1983-85) and follow-up (2001-03). The participants (n = 1049, 574 women) had a mean age of 28 ± 6 years at baseline and mean follow-up time of 27 ± 4 years. At each stage lung function (FEV(1) and FVC) and C-reactive protein (CRP) were evaluated. Change in FEV(1) (p = 0.04) and FVC (p = 0.01) was associated with baseline CRP in men but not in women. In the multiple variable analysis, CRP at baseline was associated with a decline in FEV(1) (-3.1 mL/year, 95% CI: -5.1, -0.99) and FVC (-2.5 mL/year, 95% CI: -4.4, -0.65) in men but not in women. Similarly during follow-up, change in CRP, standardised to 1SD, was associated with a decline in FEV(1) (-0.19 mL/year, 95% CI: -0.30, -0.07) and FVC (-0.11 mL/year, 95% CI: -0.22, -0.01)) in men but not in women. This prospective study confirms a stronger association between systemic inflammation and lung function decline in men than in women. This may indicate a gender difference in the mechanisms of lung function decline.

Persistent Chlamydia Pneumoniae serology is related to decline in lung function in women but not in men. Effect of persistent Chlamydia pneumoniae infection on lung function.

BACKGROUND: Chlamydia pneumoniae (C pn) infection causes an acute inflammation in the respiratory system that may become persistent, but little is known about the long-term respiratory effects of C pn infections. AIM: To estimate the long term respiratory effects of C pn with change in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) as a main outcome variable. METHODS: The study comprised of 1109 subjects (500 men and 609 women, mean age 28 ± 6 years) that participated in the Reykjavik Heart Study of the Young. Spirometry and blood samples for measurements of IgG antibodies for C pn were done at inclusion and at the end of the follow-up period (mean follow-up time 27 ± 4 years). RESULTS: Having IgG against C pn at both examinations was significantly associated to a larger decrease in FEV1 (6 mL/year) and FVC (7 mL/year) in women but not in men. In women the association between C pn and larger FEV1 decline was only found in women that smoked at baseline where having C pn IgG was associated with 10 mL/year decline compared to smokers without C pn IgG. These results were still significant after adjustment for age, smoking and change in body weight. CONCLUSION: Our results indicate that persistent C pn serology is related to increased decline in lung function in women but not in men. This effect was, however, primarily found in smoking women. This study is a further indication that the pathophysiological process leading to lung impairment may differ between men and women.

Colonic adenomas found via colonoscopy: yield and risk factors for high-grade dysplasia.

BACKGROUND AND AIMS: The adenoma-carcinoma sequence is the model for colorectal carcinoma (CRC) developing through high-grade dysplasia (HGD) to CRC. The aim was to assess prevalence and location of adenomas found during colonoscopy and risk factors for HGD. MATERIAL AND METHODS: A population-based study using all colonoscopies and polyp specimens registered between 2000 and 2004 in Iceland. Multiple logistic regression analysis was used to assess independent risk factors for HGD. RESULTS: A total of 3,315 adenomas were removed from 2,385 patients. Only 14.0% were >1 cm in size. HGD was found in 135 (4.1%) of the adenomas and tubulovillous/villous histology in 15.0%. The prevalence of adenomas in the 50- to 69-year age group was 15.5%, and 21.5% in the >or=70-year group. 60.9% of them were located distal to the splenic flexure. Independent risk factors for HGD were in the order of importance: size; multiplicity; tubulovillous/villous histology; location in rectum, and age. The prevalence of HGD in the group with an adenoma size of 0.6-1.0 cm was 4.1% and in the 40- to 69-year age group it was 3.7%. CONCLUSION: The study suggests a potential 15% yield per colonoscopy of adenomas in 50- to 69-year-olds. There is an appreciable risk of HGD in diminutive polyps and in middle age.

Natural history of functional dyspepsia: a 10-year population-based study.

BACKGROUND: Functional dyspepsia (FD) is a common disorder, but information on its natural history is limited. AIM: To study the natural history of FD as assessed by 2 criteria over a 10-year period. METHOD: A population-based study conducted by mailing a questionnaire to the same age- and gender-stratified random sample of the Icelandic population aged 18-75 in 1996 and again in 2006. FD was estimated by the Functional Dyspepsia Score List and by dyspepsia subgroups categorized into 4 groups: (1) frequent upper pain, (2) meal-related, (3) nausea or vomiting, and (4) combinations of these groups. RESULTS: FD was diagnosed in 13.9% of the subjects in the 1996 sample (11.3% male, 15.8% female) and 16.7% in 2006 (12.3% male, 20.2% female) with a significant difference between males and females in 2006. Dyspepsia subgroup criteria showed a higher prevalence than conventional FD criteria. The proportion of FD subjects in one of the dyspepsia subgroups was low. There was a significant relationship between FD and heartburn and irritable bowel syndrome. A high proportion of subjects who seek medical care have FD. CONCLUSION: FD was stable over the 10-year period, but there was turnover in symptoms and increased intensity and frequency of gastrointestinal pain. Dyspepsia subgroup criteria showed a higher prevalence than FD, which was more common in young subjects and females. FD poses a heavy burden on the health care system.

Seroprevalence of Helicobacter pylori and cagA antibodies in Iceland, Estonia and Sweden.

The public health implications from H. pylori infection are considerable but the transmission routes are largely unknown. In this study, the prevalence, patient characteristics and risk factors for Helicobacter pylori infection were comparatively investigated in Iceland, Sweden and Estonia. Blood samples were collected from 1046 subjects aged approximately 25-50 y (447 in Reykjavik, 359 in Uppsala and 240 in Tartu) for determination of antibodies to H. pylori and its cagA protein. The prevalence of H. pylori antibodies was 69% in Tartu, 36% in Reykjavik and 11% in Uppsala (p<0.0001). There was an increase in prevalence with age in Iceland and Sweden but not in Estonia. The prevalence of antibodies to the cagA protein in subjects seroreactive to H. pylori was lower in Reykjavik (36%) than in Uppsala (69%) and Tartu (62%) (p<0.0001). H. pylori infection, as determined by seroreactivity, was positively associated with smoking and BMI. Overall, socioeconomic development during the childhood period seems to be the most important factor for the prevalence of H. pylori infection. In adults, smoking may be a contributory factor.

Granulomatous ileitis in a patient with ankylosing spondylitis.

BACKGROUND: A 21-year-old white male with a 3-year history of back pain presented with a 6-month history of weight loss (without significant gastrointestinal symptoms), lethargy and left hip pain, and diarrhea that had lasted 4 days. INVESTIGATIONS: Barium follow-through, upper and lower gastrointestinal endoscopy and biopsies, capsule enteroscopy, CT of the chest and abdomen, measurement of the concentration of fecal calprotectin, intestinal absorption permeability test and wireless capsule endoscopy. DIAGNOSIS: Ankylosing spondylitis associated with ileitis of spondylarthropathy. MANAGEMENT: Sulfasalazine and elemental diet, steroids, physiotherapy and bilateral hip replacement.

Gender differences in the association between C-reactive protein, lung function impairment, and COPD.

Individuals with COPD have systemic inflammation that can be assessed by measuring C-reactive protein (CRP). In this paper we evaluated whether CRP is related to COPD, lung function and rate of lung function decline. We included 1237 randomly selected subjects (mean age 42, range 28-56 years) from three centers in the European Community Respiratory Health Survey: Reykjavik, Uppsala and Tartu. CRP was measured at the end of the follow-up (mean 8.3 years) and the values were divided into 4 quartiles. Fifty-three non-asthmatic subjects fulfilled spirometric criteria for COPD (FEV1/FVC < 70%). COPD occurred more often in the 4th CRP quartile (OR (95% CI) 3.21 (1.13-9.08)) after adjustment for age, gender, body weight and smoking. High CRP levels were related to lower FEV1 values in both men (-437 (-596, -279) mL) and women (-144 (-243, -44) mL). The negative association between CRP and FEV1 was significantly larger in men than women (p = 0.04). The decline in FEV1 was larger (16 (5, 27) mL) in men with high CRP levels whereas no significant association between CRP and FEV1 decline was found in women. Higher CRP values are significantly associated with COPD and lower lung function in men and women. In men higher CRP values are related to a larger decline in FEV1.

Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease.

BACKGROUND & AIMS: It has been variably suggested that nonselective NSAIDs and cyclooxygenase (COX)-2 selective inhibitors aggravate or ameliorate clinical disease activity in patients with inflammatory bowel disease. We assessed the effect of these drugs in patients with inflammatory bowel disease (n = 209) and the possible mechanisms. METHODS: First, patients with quiescent Crohn's disease and ulcerative colitis received the non-NSAID analgesic acetaminophen (n = 26) and the conventional NSAIDs naproxen (n = 32), diclofenac (n = 29), and indomethacin (n = 22) for 4 weeks. The Harvey-Bradshaw index was used to define relapse. Second, to assess the mechanism of relapse, intestinal inflammation was quantitated (fecal calprotectin) before and during treatment (20 patients/group) with acetaminophen, naproxen (topical effect, COX-1 and -2 inhibitor), nabumetone (COX-1 and -2 inhibitor), nimesulide (selective COX-2 inhibitor), and low-dose aspirin (selective COX-1 inhibition). RESULTS: Nonselective NSAIDs were associated with a 17%-28% relapse rate within 9 days of ingestion. No patient had an early relapse on acetaminophen, nimesulide, or aspirin, whereas those on naproxen and nabumetone (20%) experienced relapse. These clinical relapses were associated with escalating intestinal inflammatory activity. CONCLUSIONS: NSAID ingestion is associated with frequent and early clinical relapse of quiescent inflammatory bowel disease, and the mechanism appears to be due to dual inhibition of the COX enzymes. Selective COX-2 inhibition with nimesulide and COX-1 inhibition with low-dose aspirin appear to be well-tolerated in the short-term.

Effects of 5 years of treatment with rabeprazole or omeprazole on the gastric mucosa.

BACKGROUND: Prolonged gastric acid suppression leads to hypergastrinaemia, which promotes hyperplasia of the enterochromaffin-like (ECL) cells of the oxyntic mucosa. The objective was to determine the effects of 5 years of treatment with rabeprazole or omeprazole on the gastric mucosa. METHODS: Two hundred and forty-three patients received rabeprazole (20 mg or 10 mg) or omeprazole (20 mg) once daily for up to 5 years, for gastro-oesophageal reflux disease and 51% completed the whole 5 year period. Gastric biopsy specimens were taken and examined for gastritis, Helicobacter pylori infection, and ECL cell status. FINDINGS: H. pylori infection in the gastric corpus was more common than in the antrum, and remained constant, whereas antral H. pylori infection became less common as the study progressed. H. pylori infection was a highly significant predictor of higher gastritis scores, which were similar among the three treatment groups. ECL cell hyperplasia occurred in a minority of patients, and was associated with serum gastrin concentrations. No ECL cell dysplasia or tumours were observed. There were no significant differences among the treatment groups in gastritis or ECL cell hyperplasia grades. INTERPRETATION: This study has confirmed the link between ECL cell hyperplasia and elevated serum gastrin concentrations, but has found no evidence that this progresses to high grades of hyperplasia during 5 years of treatment with rabeprazole or omeprazole.

Subclinical intestinal inflammation: an inherited abnormality in Crohn's disease relatives?

BACKGROUND & AIMS: One approach to unraveling the genetics of complex inherited disease, such as Crohn's disease, is to search for subclinical disease markers among unaffected family members. We assessed the possible presence, prevalence, and inheritance pattern of subclinical intestinal inflammation in apparently healthy relatives of patients with Crohn's disease. METHODS: A total of 49 patients with Crohn's disease, 16 spouses, and 151 (58%) of 260 available first-degree relatives underwent a test for intestinal inflammation (fecal calprotectin concentration). The mode of inheritance was assessed from 36 index patients (by variance component analysis) when more than 50% of relatives were studied. RESULTS: Fecal calprotectin concentrations in patients with Crohn's disease (47 mg/L; confidence interval [CI], 27-95 mg/L) and relatives (11 mg/L; CI, 9-14 mg/L) differed significantly (P < 0.0001) from controls (4 mg/L; CI, 3-5 mg/L), whereas that of the spouses did not (4 mg/L; CI, 3-6 mg/L; P > 0.5). Fecal calprotectin concentration was increased in 49% of all relatives studied. The increased fecal calprotectin concentration among the relatives of the 36 index patients had an inheritance pattern that was most consistent with an additive inheritance pattern. CONCLUSIONS: There is a high prevalence of subclinical intestinal inflammation in first-degree relatives of patients with Crohn's disease that conforms best to an additive inheritance pattern. The genetic basis for this abnormality may represent a risk factor for Crohn's disease.

Subclinical intestinal inflammation and sacroiliac changes in relatives of patients with ankylosing spondylitis.

BACKGROUND & AIMS: It has been suggested that subclinical intestinal inflammation plays a pathogenic role in the spondylarthropathy of ankylosing spondylitis (AS). We assessed the possible presence and inheritance pattern of subclinical intestinal inflammation in first-degree relatives of patients with AS. The relationship between this inflammation and the subjects' HLA-B27 genotype as well as computerized tomographic sacroiliac abnormalities was also assessed. METHODS: A total of 124 of 213 (58%) available first-degree relatives of 47 patients with AS in Iceland underwent investigation for intestinal inflammation (fecal calprotectin concentration), HLA-B27 genotyping, and computerized tomography of the sacroiliac joints. RESULTS: A total of 41% of the first-degree relatives had subclinical intestinal inflammation, whereas 15 of 17 spouses were normal. Variance components analyses suggest that the inheritance pattern of this inflammation is affected by a major additive gene. Some sacroiliac changes, suggestive of early AS, differed significantly between subjects with and without subclinical intestinal inflammation (mean diameter of subchondral cysts [2.9 vs. 1.2 mm; P = 0.026] and blurring of joint margins [9 of 44 (20%) vs. 1 of 41 (2%); P = 0.02]). Intestinal inflammation and sacroiliac changes did not relate to the subjects' HLA-B27 status. CONCLUSIONS: Many first-degree relatives of patients with AS appear to have an inherited abnormality that leads to subclinical intestinal inflammation. The association between the presence of this inflammation and the sacroiliac changes suggests that it may play a pathogenic role in the spondylarthropathy of AS.

Trends in peptic ulcer morbidity and mortality in Iceland.

A cohort pattern has been demonstrated for ulcer mortality and perforation, pointing to a role of early life factors, while only a period-related decrease has been observed in elective ulcer surgery, which reflects uncomplicated ulcer. The aim of this article was to study whether the susceptibility to peptic ulcer disease is determined early in life, as reflected in a cohort pattern consistent for all ulcer manifestations. The subjects were all patients treated surgically for peptic ulcer (perforations 1962-1990; bleedings 1971-1990; elective surgery 1971-1990) and all deaths from peptic ulcer (perforations and other ulcer deaths 1951-1989) in Iceland. Age-specific incidence and mortality were analyzed graphically by year of birth (cohort) and by year of event (period). The effects of cohort and period on incidence and mortality were analyzed by Poisson regression. Ulcer perforation and bleeding, operative incidence, and mortality, showed a rise and subsequent fall in successive generations, with the highest risks observed in the subjects born after the turn of the 20(th) century. This was confirmed by statistical analyses showing highly significant cohort effects (P <.001) and no period effects. A cohort pattern was similarly found for elective ulcer surgery (P <.001), as well as a period-related decrease across age groups (P <.001). Ulcer complications, ulcer deaths, and uncomplicated ulcer were particularly common in specific generations carrying a high risk of peptic ulcer throughout their lives. These were the generations with the highest prevalence of H. pylori antibodies, the subjects born after the turn of the century at a time of maximum crowding and poor hygiene in Iceland due to the industrial revolution.