Malin Inghammar

COPD and the Risk of Tuberculosis - A Population-Based Cohort Study

Background Both chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) primarily affect the lungs and are major causes of morbidity and mortality worldwide. COPD and TB have common risk factors such as smoking, low socioeconomic status and dysregulation of host defence functions. COPD is a prevalent co-morbid condition, especially in elderly with TB but in contrast to other diseases known to increase the risk of TB, relatively little is known about the specific relationship and impact from COPD on TB-incidence and mortality. Methods and Findings All individuals ≥40 years of age, discharged with a diagnosis of COPD from Swedish hospitals 1987–2003 were identified in the Swedish Inpatient Register (n = 115,867). Records were linked to the Swedish Tuberculosis Register 1989–2007 and the relative risk of active TB in patients with COPD compared to control subjects randomly selected from the general population (matched for sex, year of birth and county of residence) was estimated using Cox regression. The analyses were stratified by year of birth, sex and county of residence and adjusted for immigration status, socioeconomic status (SES) and inpatient co-morbidities previously known to increase the risk of TB. COPD patients had a three-fold increased hazard ratio (HR) of developing active TB (HR 3.0 (95% confidence interval 2.4 to 4.0)) that was mainly dependent on an increased risk of pulmonary TB. In addition, logistic regression estimates showed that COPD patients who developed active TB had a two-fold increased risk of death from all causes within first year after the TB diagnosis compared to the general population control subjects with TB (OR 2.2, 95% confidence interval 1.2 to 4.1). Conclusions This population-based study comprised of a large number of COPD patients shows that these patients have an increased risk of developing active TB compared to the general population. The results raise concerns that the increasing global burden of COPD will increase the incidence of active TB. The underlying contributory factors need to be disentangled in further studies.

Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock

IntroductionRapid detection of, and optimized treatment for, severe sepsis and septic shock is crucial for successful outcome. Heparin-binding protein (HBP), a potent inducer of increased vascular permeability, is a potentially useful biomarker for predicting outcome in patients with severe infections. Our aim was to study the systemic release and dynamics of HBP in the plasma of patients with severe sepsis and septic shock in the ICU.MethodsA prospective study was conducted of two patient cohorts treated in the ICU at Karolinska University Hospital Huddinge in Sweden. A total of 179 patients was included, of whom 151 had sepsis (126 with septic shock and 25 patients with severe sepsis) and 28 a non-septic critical condition. Blood samples were collected at five time points during six days after admission.ResultsHBP levels were significantly higher in the sepsis group as compared to the control group. At admission to the ICU, a plasma HBP concentration of ≥15 ng/mL and/or a HBP (ng/mL)/white blood cell count (109/L) ratio of >2 was found in 87.2% and 50.0% of critically ill patients with sepsis and non-septic illness, respectively. A lactate level of >2.5 mmol/L was detected in 64.9% and 56.0% of the same patient groups. Both in the sepsis group (n = 151) and in the whole group (n = 179), plasma HBP concentrations at admission and in the last measured sample within the 144 hour study period were significantly higher among 28-day non-survivors as compared to survivors and in the sepsis group, an elevated HBP-level at baseline was associated with an increased case-fatality rate at 28 days.ConclusionsPlasma HBP levels were significantly higher in patients with severe sepsis or septic shock compared to patients with a non-septic illness in the ICU. HBP was associated with severity of disease and an elevated HBP at admission was associated with an increased risk of death. HBP that rises over time may identify patients with a deteriorating prognosis. Thus, repeated HBP measurement in the ICU may help monitor treatment and predict outcome in patients with severe infections.

Short term effects of incubator covers on quiet sleep in stable premature infants

Incubator covers are increasingly being used in neonatal care as part of minimal disturbance strategies. The aim of this study was to examine possible effects of incubator covers on sleep patterns in stable premature infants. Quiet sleep (QS) can be investigated by amplitude‐integrated electroencephalography (aEEG) at 32‐34 wk gestational age. In nine premature infants (gestational ages 26‐32 wk, median 29) QS periods were measured at a postconceptional age of 32‐34 wk (median 34) during two consecutive 24 h periods, one period with a padded dark cover over the incubator and one period without the cover, in a randomized order. There were no significant differences between the two 24 h periods (with incubator cover and without cover, respectively) regarding the duration of the QS periods, the percentage of QS of the total recording time (%QS) or the duration of QS intervals. However, there was a positive correlation between postnatal age in days and the mean duration of QS periods when incubator covers were used (r= 0.90, p= 0.001). When the covers were used there was a difference between the girls and the boys in the duration of QS intervals (p= 0.032); the QS intervals increased in the five girls from median (range) 63.2 (49.4–94.6) min to 77.2 (59.3–100.9) min (p= 0.043). There was no difference in the duration of QS periods between girls and boys.

Invasive pneumococcal disease in patients with an underlying pulmonary disorder.

Chronic pulmonary disease is a recognized risk factor for invasive pneumococcal disease (IPD). However, previous studies have often not been large enough to allow detailed analyses of less prevalent pulmonary diseases, and findings regarding case fatality have been inconsistent. We examined the associations between an underlying pulmonary disease and IPD, and the impact of these diseases on the case fatality rate. Patients with IPD ≥18 years of age, between 1990 and 2008, were identified in microbiological databases. The associations between IPD and the pulmonary diseases were assessed using conditional logistic regression, comparing IPD cases to ten control subjects per case, randomly selected from the general population (matched for gender, year of birth and county of residence). Adjustments were made for other co-morbidities, level of education and socio-economic status, 4085 cases of IPD and 40 353 controls were identified. A more than four-fold increased risk of IPD was seen in chronic obstructive pulmonary disease, a doubled risk in asthma and a five-fold increased risk in subjects with pulmonary fibrosis. In univariate analysis, sarcoidosis and bronchiectasis were associated with a two-fold to seven-fold increase in the risk of IPD, but there was no statistical support for the associations when adjustments for confounders were made. No increased risk was seen in subjects with a history of pneumoconiosis or allergic alveolitis. The mortality following IPD was not increased in patients with chronic obstructive pulmonary disease, asthma, pulmonary fibrosis or bronchiectasis. Several chronic pulmonary diseases increase the risk of IPD but mortality following IPD seems not to be affected.

Validation of a COPD diagnosis from the Swedish Inpatient Registry.

Aims: The Swedish National Inpatient Registry is an important source of data for numerous epidemiological studies, amongst them studies on chronic obstructive pulmonary disease (COPD). General validation studies indicate that in general 85–95% of diagnoses reported are correct, but this is not true for all groups of diseases, why specific validation studies are of great importance. Methods: Charts from 374 individuals discharged with a COPD diagnosis between 2000–07 from two central hospitals and two university hospitals in the county of Skåne were validated against the original medical files. Criteria for the degree of certainty of the COPD diagnosis were predefined and the association between predictors of diagnostic probability and the level of certainty was assessed using an ordinal logistic regression model. Results: According to the Global Initiative for Chronic Obstructive Lung Disease criteria, 21.7% of the diagnosis were classified as proven COPD, 35.5% were classified as probable, another 34.0% as possible COPD, 2.1% were classified as having an uncertain diagnosis, and 7.0% as an unlikely COPD diagnosis. Age category (adjusted ORs: 60–79 years, 2.6, 95% CI 1.2–5.4; ≥80 years, 1.6, 95% CI 0.7–3.3) and discharge from a non-surgical department (adjusted OR: 1.7, 95% CI 1.1–2.8) were significantly associated with higher level of diagnostic certainty. Conclusions: A COPD diagnoses from the Swedish Inpatient Registry is of acceptable validity for epidemiological research. The degree of certainty of the diagnosis varies but less than 10% were considered as misclassified or having an uncertain COPD diagnosis.

Fever in the Emergency Department Predicts Survival of Patients With Severe Sepsis and Septic Shock Admitted to the Icu

Objectives: To study the prognostic value of fever in the emergency department in septic patients subsequently admitted to the ICU. Design: Observational cohort study from the Swedish national quality register for sepsis. Setting: Thirty ICU’s in Sweden. Patients: Two thousand two hundred twenty-five adults who were admitted to an ICU within 24 hours of hospital arrival with a diagnosis of severe sepsis or septic shock were included. Interventions: None. Measurements and Main Results: Body temperature was measured and classified according to four categories (< 37°C, 37–38.29°C, 38.3–39.5°C, ≥ 39.5°C). The main outcome was in-hospital mortality. Odds ratios for mortality according to body temperature were estimated using multivariable logistic regression. Subgroup analyses were conducted according to age, sex, underlying comorbidity, and time to given antibiotics. Overall mortality was 25%. More than half of patients had a body temperature below 38.3°C. Mortality was inversely correlated with temperature and decreased, on average, more than 5% points per °C increase, from 50% in those with the lowest temperatures to 9% in those with the highest. Increased body temperature in survivors was also associated with shorter hospital stays. Patients with fever received better quality of care, but the inverse association between body temperature and mortality was robust and remained consistent after adjustment for quality of care measures and other factors that could have confounded the association. Among vital signs, body temperature was best at predicting mortality. Conclusions: Contrary to common perceptions and current guidelines for care of critically ill septic patients, increased body temperature in the emergency department was strongly associated with lower mortality and shorter hospital stays in patients with severe sepsis or septic shock subsequently admitted to the ICU.

Oral fluoroquinolone use and serious arrhythmia: bi-national cohort study

Objective To evaluate if oral fluoroquinolone use is associated with an increased risk of serious arrhythmia. Design Bi-national cohort study, linking register data on filled prescriptions, cases of serious arrhythmia, and patient characteristics. Setting Denmark, 1997-2011; Sweden, 2006-13. Participants The study cohort was derived from a source population of all Danish and Swedish adults, aged 40 to 79 years. 909 656 courses of fluoroquinolone use (ciprofloxacin 82.6%, norfloxacin 12.1%, ofloxacin 3.2%, moxifloxacin 1.2%, and other fluoroquinolones 0.9%) and 909 656 courses of penicillin V use, matched 1:1 on propensity score, were included. Main outcome measure The main outcome was risk of serious arrhythmia (fatal and non-fatal), comparing courses of fluoroquinolone use with courses of penicillin V use (an antibiotic with no pro-arrhythmic effect). The risk period of interest was current use, defined as days 0-7 of treatment. Subgroup analyses were conducted according to country, sex, age, underlying cardiovascular disease, concomitant use of drugs known to increase the risk of torsades de pointes, fluoroquinolone type, and levels of arrhythmia risk score. Results 144 cases of serious arrhythmia occurred during follow-up, 66 among current fluoroquinolone users (incidence rate 3.4 per 1000 person years) and 78 among current penicillin users (4.0 per 1000 person years); comparing oral fluoroquinolone treatment with penicillin V, the rate ratio was 0.85 (95% confidence interval 0.61 to 1.18). Compared with penicillin V, the absolute risk difference was −13 (95% confidence interval −35 to 16) cases of serious arrhythmia per 1 000 000 courses of fluoroquinolones. The risk of serious arrhythmia was not statistically significantly increased in any of the subgroups, including analyses by fluoroquinolone type. Conclusions Contrary to previous reports, oral fluoroquinolone treatment was not associated with an increased risk of serious arrhythmia in the general adult populations of Denmark and Sweden. Given the statistical power of the study, even small increases in relative and absolute risk could be ruled out. Since ciprofloxacin was the most commonly used fluoroquinolone in our study, we cannot exclude that intraclass differences influence the risk of serious arrhythmia associated with other less frequently used fluoroquinolones.

Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study

Abstract Objective To investigate whether oral fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection. Design Nationwide historical cohort study using linked register data on patient characteristics, filled prescriptions, and cases of aortic aneurysm or dissection. Setting Sweden, July 2006 to December 2013. Participants 360 088 treatment episodes of fluoroquinolone use (78%ciprofloxacin) and propensity score matched comparator episodes of amoxicillin use (n=360 088). Main outcome measures Cox regression was used to estimate hazard ratios for a first diagnosis of aortic aneurysm or dissection, defined as admission to hospital or emergency department for, or death due to, aortic aneurysm or dissection, within 60 days from start of treatment. Results Within the 60 day risk period, the rate of aortic aneurysm or dissection was 1.2 cases per 1000 person years among fluoroquinolone users and 0.7 cases per 1000 person years among amoxicillin users. Fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection (hazard ratio 1.66 (95% confidence interval 1.12 to 2.46)), with an estimated absolute difference of 82 (95% confidence interval 15 to 181) cases of aortic aneurysm or dissection by 60 days per 1 million treatment episodes. In a secondary analysis, the hazard ratio for the association with fluoroquinolone use was 1.90 (1.22 to 2.96) for aortic aneurysm and 0.93 (0.38 to 2.29) for aortic dissection. Conclusions In a propensity score matched cohort, fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection. This association appeared to be largely driven by aortic aneurysm.

A nationwide cohort study of the risk of chronic obstructive pulmonary disease in coeliac disease.

Abstract.  Ludvigsson JF, Inghammar M, Ekberg M, Egesten A (Örebro University Hospital, Örebro; Karolinska Institutet, Stockholm; and Lund University, Skåne University Hospital, Lund, Sweden). A nationwide cohort study of the risk of chronic obstructive pulmonary disease in coeliac disease. J Intern Med 2012; 271: 481–489.

Impaired pulmonary function and the risk of tuberculosis: a population-based cohort study

To the Editors: It is well known that pulmonary tuberculosis (TB) can cause lung impairment leading to chronic obstructive pulmonary disease (COPD) 1, but less is known to what extent impaired lung function increases the risk of TB. A case–control study from the UK found patients with emphysema to have a three-fold increased risk of TB, adjusted for smoking and the use of corticosteroids 2. A cohort study from Denmark found moderate-to-severe COPD to be associated with a two- to three-fold increased risk of hospitalisation with TB 3. We have previously shown that patients hospitalised with COPD have a three-fold increased risk of active TB compared with population controls 4. In the present study, we examine the risk of active TB in relation to lung function in a cohort who underwent spirometry in 1974–1992. Between 1974 and 1992, 22,444 males and 10,902 females, born 1921–1949, participated in a health screening programme, the Malmo Preventive Project. Complete birth cohorts, born in pre-specified years, from the city of Malmo were invited; the overall participation proportion was ∼70% 5. The screening included physical examination, spirometry, blood samples and assessment of lifestyle factors by means of a self-administered questionnaire. Some questions varied between the cohorts. We excluded 4,413 individuals because of missing spirometry data; 26 individuals were excluded because of missing data on either body mass index (BMI), smoking or immigration status, leaving a total of 28,907 individuals in final analysis (21,174 males and 7,733 females). BMI as was calculated as mass/height2 (in kg·m−2). Individuals were regarded as having diabetes mellitus if they answered positively to the question “Do you have diabetes mellitus?” or their fasting blood glucose level was ≥6.1 mmol·L−1. Around 96% of the cohort (n = 27,789) answered questions on alcohol. Individuals …