Survival in severe alpha-1-antitrypsin deficiency (PiZZ)

<p>Abstract</p> <p>Background</p> <p>Previous studies of the natural history of alpha-1-antitrypsin (AAT) deficiency are mostly based on highly selected patients. The aim of this study was to analyse the mortality of PiZZ individuals.</p> <p>Methods</p> <p>Data from 1339 adult PiZZ individuals from the Swedish National AAT Deficiency Registry, followed from 1991 to 2008, were analysed. Forty-three percent of these individuals were identified by respiratory symptoms (respiratory cases), 32% by liver diseases and other diseases (non-respiratory cases) and 25% by screening (screened cases). Smoking status was divided into two groups: smokers 737 (55%) and 602 (45%) never-smokers.</p> <p>Results</p> <p>During the follow-up 315 individuals (24%) died. The standardised mortality rate (SMR) for respiratory cases was 4.70 (95% Confidence Interval (CI) 4.10-5.40), 3.0 (95%CI 2.35-3.70) for the non-respiratory cases and 2.30 (95% CI 1.46-3.46) for the screened cases. The smokers had a higher mortality risk than never-smokers, with a SMR of 4.80 (95%CI 4.20-5.50) for the smokers and 2.80(95%CI 2.30-3.40) for the never-smokers. The Rate Ratio (RR) was 1.70 (95% CI 1.35-2.20). Also among the screened cases, the mortality risk for the smokers was significantly higher than in the general Swedish population (SMR 3.40 (95% CI 1.98-5.40).</p> <p>Conclusion</p> <p>Smokers with severe AAT deficiency, irrespective of mode of identification, have a significantly higher mortality risk than the general Swedish population.</p

Prevalence of genetic polymorphisms in the promoter region of the alpha-1 antitrypsin (SERPINA1) gene in chronic liver disease: a case control study

Contains fulltext : 89639.pdf (publisher's version ) (Open Access)BACKGROUND: Alpha-1 antitrypsin (A1AT) deficiency, caused by the Z allele (p.E342K) and S allele (p.E264V) in the SERPINA1 gene, can induce liver and pulmonary disease. Different mechanisms appear to be responsible for the pathogenesis of these divergent disease expressions. The c.-1973T >C polymorphism located in the SERPINA1 promoter region is found more frequent in A1AT deficiency patients with liver disease compared to patients with pulmonary disease, but data are lacking regarding contribution to the development of liver diseases caused by other aetiologies. AIM: To study the prevalence of c.-1973T >C, Z allele and S allele in a cohort of patients with liver disease of various aetiologies compared with healthy controls and to evaluate its effect on disease progression. METHODS: A total of 297 patients with liver disease from various aetiologies and 297 age and gender matched healthy controls were included. The c.-1973T >C polymorphism and Z and S alleles of the SERPINA1 gene were analyzed by real-time PCR. RESULTS: c.-1973T >C was similarly distributed between patients with liver disease of various origins and healthy controls. Furthermore, the distribution of c.-1973T >C was independent from aetiology subgroup. In patients with liver disease mean ages at of onset of liver disease were 44.4, 42.3 and 40.7 years for the c.-1973 T/T, T/C and C/C genotype respectively (NS). S allele heterozygosity was increased in patients with drug induced liver injury (DILI), (OR 4.3; 95%CI 1.1-17.2). CONCLUSION: In our study, c.-1973T >C polymorphism was not a risk factor for liver disease of various aetiologies. In addition, S allele heterozygosity might contribute to the development of DILI

The risk of burn injury during long-term oxygen therapy: a 17-year longitudinal national study in Sweden

Hanan A Tanash,1 Fredrik Huss,2,3 Magnus Ekstr&ouml;m41Department of Respiratory Medicine and Allergology, Sk&aring;ne University Hospital, Lund University, Lund, 2Department of Surgical Sciences, Plastic Surgery, Uppsala University, 3Burn Center, Department of Plastic and Maxillofacial Surgery, University Hospital of Uppsala, Uppsala, 4Department of Clinical Sciences, Division of Respiratory Medicine&nbsp;&amp;&nbsp;Allergology, Lund University, Lund,&nbsp;SwedenBackground: Long-term oxygen therapy (LTOT) improves the survival time in hypoxemic chronic obstructive pulmonary disease. Despite warnings about potential dangers, a considerable number of patients continue to smoke while on LTOT. The incidence of burn injuries related to LTOT is unknown. The aim of this study was to estimate the rate of burn injury requiring health care contact during LTOT.Methods: Prospective, population-based, consecutive cohort study of people starting LTOT from any cause between January 1, 1992 and December 31, 2009 in the Swedish National Register of Respiratory Failure (Swedevox).Results: In total, 12,497 patients (53% women) were included. The mean (standard deviation) age was 72&plusmn;9 years. The main reasons for starting LTOT were chronic obstructive pulmonary disease (75%) and pulmonary fibrosis (15%). Only 269 (2%) were active smokers when LTOT was initiated. The median follow-up time to event was 1.5 years (interquartile range, 0.55&ndash;3.1). In total, 17 patients had a diagnosed burn injury during 27,890 person-years of LTOT. The rate of burn injury was 61 (95% confidence interval, 36&ndash;98) per 100,000 person-years. There was no statistically significant difference in the rate of burn injury between ever-smokers and never-smokers, or between men and women.Conclusion: The rate of burn injuries in patients on LTOT seems to be low in Sweden. The strict requirements in Sweden for smoking cessation before LTOT initiation may contribute to this finding.Keywords: respiratory failure, oxygen, fire, burn, mortality, smokin

Risk of cancer after lung transplantation for COPD

Magnus Ekstr&ouml;m,1 Gerdt C Riise,2 Hanan A Tanash3 1Department of Clinical Sciences, Division of Respiratory Medicine &amp; Allergology, Lund University, Lund, Sweden; 2Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 3Department of Respiratory Medicine, Sk&aring;ne University Hospital, Lund University, Malm&ouml;, Sweden Background: The risk of cancer is increased and affects survival after lung transplantation (LTx), but has not been well characterized in COPD. We aimed to evaluate the incidence and prognosis of cancer following LTx for COPD.Methods: A prospective, population-based study of patients undergoing LTx for end-stage COPD at the two transplantation centers in Sweden between 1990-2013, with follow-up for incident cancer and death, using national registers. The excess risk of cancer was calculated as standardized incidence ratios compared with the general population matched for age, sex, and calendar year. Risk factors for cancer were analyzed using Fine-Gray regression, and survival after cancer diagnosis with Kaplan&ndash;Meier.Results: In total, 331 patients (mean age 55.4 years; 64% women; 97% former smokers) were included. At a median follow-up of 2.8 years, 35% of patients had developed cancer and the risk was increased more than 10-fold ([95% CI] 8.1-11.8). The highest excess risks were for non-Hodgkin lymphoma (20.8-66.7), skin cancer (20.3-35.2), lung (11.7-31.2), liver (3.6-51.6), and colorectal cancer (6.1-19.5). Median survival was longer for skin cancer (8 years; 95% CI, 3-15) compared with non-skin cancer (4 years; 95% CI, 2.8-4.8; p&lt;0.001).Conclusion: The cancer risk is markedly increased after LTx for COPD. It could not be predicted by the factors evaluated, but contributed significantly to a negative prognosis. Keywords: cancer, COPD, lung transplantation, severe alpha-1-antitrypsin deficiency, survival&nbsp

Survival in the Swedish cohort with alpha-1-antitrypsin deficiency, up to the age of 43&ndash;45 years

Behrouz Mostafavi, Eeva Piitulainen, Hanan A Tanash Department of Respiratory Medicine and Allergology, Sk&aring;ne University Hospital, Lund University, Malm&ouml;, Sweden Background: Alpha-1-antitrypsin deficiency (AATD) is a hereditary disorder. AATD is a known risk factor for the development of emphysema and liver disease. A cohort of severe (PiZZ) and moderate (PiSZ) AAT-deficient newborn infants was identified by the Swedish national neonatal AAT screening in 1972&ndash;1974 and has been followed up since birth. Our aim was to study survival in this cohort up to 43&ndash;45 years of age in comparison with the general Swedish population.Methods: Data from 127 PiZZ, 2 PiZnull, 54 PiSZ, and 1 PiSnull subjects, who were identified by the neonatal screening in 1972&ndash;1974, were included in the study. To compare death rates in the PiZZ and PiSZ individuals with the general Swedish population, a standardized mortality ratio (SMR) was calculated as the ratio of observed to expected deaths.Results: Seven PiZZ subjects died during the follow-up, to be compared with an expected 3.66 deaths for the general population, giving an SMR of 1.91 (95% CI 0.77&ndash;3.94). Four PiSZ subjects died compared to an expected 1.53 deaths, giving an SMR of 2.61 (95% CI 0.71&ndash;6.71). The cumulative probability of survival up to the age of 45 years was 94% (95% CI 90%&ndash;98%) for the study population. Six deaths occurred before the age of 8 years.Conclusion: Up to 43&ndash;45 years of age, there was no difference in survival between PiZZ and PiSZ individuals in comparison with the Swedish general population. The majority of deaths occurred during childhood. Keywords: alpha-1-antitrypsin deficiency, causes of death, screening, survival &nbsp

Health status and lung function in the Swedish alpha 1-antitrypsin deficient cohort, identified by neonatal screening, at the age of 37-40 years

Eeva Piitulainen, Behrouz Mostafavi, Hanan A Tanash Department of Respiratory Medicine and Allergology, Sk&aring;ne University Hospital, Lund University, Malm&ouml;, Sweden Background: Severe alpha 1-antitrypsin (AAT) deficiency (genotype PiZZ) is a well-known risk factor for COPD. A cohort of PiZZ and PiSZ individuals was identified by the Swedish national neonatal AAT screening program in 1972&ndash;1974 and followed up regularly since birth. Our aim was to study the lung function, respiratory symptoms and health status at the age of 38 years in comparison with a random sample of control subjects selected from the&nbsp;population registry.Methods: The study group included 120 PiZZ, 46 PiSZ and 164 control subjects (PiMM), who answered a questionnaire on smoking habits and symptoms and the Saint George Respiratory Questionnaire (SGRQ) on quality of life. A total of 89 PiZZ, 33 PiSZ and 92 PiMM subjects underwent spirometry.Results: Four percent of the PiZZ, 2% of the PiSZ and 12% of the control subjects were current smokers (P=0.008), and 17% of the PiZZ, 9% of the PiSZ and 21% of the control subjects had stopped smoking. The PiZZ current smokers had a significantly higher (ie, poorer) median activity score according to the SGRQ than the PiZZ never-smokers (P=0.032). The PiMM current smokers had significantly higher activity score (P&lt;0.001), symptom score (P&lt;0.001), and total score (P=0.001) according to the SGRQ than the PiMM never-smokers. The PiZZ current smokers had a significantly lower postbronchodilator forced expiratory volume in 1 second (FEV1)% of predicted value (P=0.019) and FEV1/forced vital capacity (FVC) ratio (P=0.032) than the PiZZ never-smokers. The proportion of subjects with a FEV1/FVC ratio of &lt;0.70, indicating COPD, was significantly higher in the PiZZ current smokers than in the PiZZ never-smokers (P=0.001). Among the PiSZ and PiMM subjects, the differences in lung function between the smoking subgroups were insignificant.Conclusion: PiZZ current smokers were found to have signs of COPD before 40 years of age. Smoking is less common among the AAT-deficient subjects identified by neonatal screening than among their peers in the general population. Keywords: alpha 1-antitrypsin deficiency, health status, lung function, COPD, screening, smokin

Burn injury during long-term oxygen therapy in Denmark and Sweden: the potential role of smoking

Hanan A Tanash,1 Thomas Ringbaek,2 Fredrik Huss,3,4 Magnus Ekstr&ouml;m1 1Department of Respiratory&nbsp;Medicine, Sk&aring;ne University Hospital,&nbsp;Lund University, Lund, Sweden; 2Respiratory&nbsp;Department, Hvidovre&nbsp;Hospital, Copenhagen, Denmark; 3Department of Surgical Sciences, Plastic Surgery, 4Department of Plastic and Maxillofacial Surgery, Burn Center, Uppsala University Hospital, Uppsala, Sweden Background: Long-term oxygen therapy (LTOT) increases life expectancy in patients with COPD and severe hypoxemia. Smoking is the main cause of burn injury during LTOT. Policy regarding smoking while on LTOT varies between countries. In this study, we compare the incidence of burn injury that required contact with a health care specialist, between Sweden (a&nbsp;country with a strict policy regarding smoking while on LTOT) and Denmark (a country with less strict smoking policy). Methods: This was a population-based, cohort study of patients initiating LTOT due to any cause in Sweden and Denmark. Data on diagnoses, external causes, and procedures were obtained from the Swedish and Danish National Patient Registers for inpatient and outpatient care. Patients were followed from January 1, 2000, until the first of the following: LTOT withdrawal, death, or study end (December 31, 2009). The primary end point was burn injury during LTOT. Results: A total of 23,741 patients received LTOT in Denmark and 7,754 patients in Sweden. Most patients started LTOT due to COPD, both in Sweden (74%) and in Denmark (62%). The rate of burn injury while on LTOT was higher in Denmark than in Sweden; 170 (95% confidence interval [CI], 126&ndash;225) vs 85 (95% CI, 44&ndash;148) per 100,000 person-years; rate ratio 2.0 (95%&nbsp;CI, 1.0&ndash;4.1). The risk remained higher after adjustment for gender, age, and diagnosis in multivariate Cox regression, hazard ratio 1.8 (95% CI, 1.0-3.5). Thirty-day mortality after burn injury was 8% in both countries. Conclusion: Compared to Sweden, the rate of burn injury was twice as high in Denmark where smoking is not a contraindication for prescribing LTOT. Keywords: burn injury, COPD, long-term oxygen therapy, smokin

Cause-specific mortality in individuals with severe alpha 1-antitrypsin deficiency in comparison with the general population in Sweden

Hanan A Tanash,1 Magnus Ekstr&ouml;m,2 Philippe Wagner,3 Eeva Piitulainen1 1Department of Respiratory Medicine, Sk&aring;ne University Hospital, 2Department of Respiratory Medicine, Blekinge Hospital Karlskrona, Lund University, Lund, 3Centre for Clinical Research, V&auml;stmanland, Uppsala University, Uppsala, Sweden Background: Severe alpha 1-antitrypsin deficiency (PiZZ) predisposes to morbidity and mortality due to early-onset emphysema and liver disease. The risk of death from other causes, including cardiovascular disease and cancer, has not been well investigated. We aimed to analyze cause-specific mortality in PiZZ individuals compared with the general Swedish population. Methods: Data on 1,561 PiZZ individuals from the Swedish National AAT Deficiency Register, prospectively followed from 1991 to 2014, were analyzed. Causes of death according to the Swedish National Causes of Death Register for the study group were compared with those for the general Swedish population matched for age, sex, and calendar year, with the excess mortality expressed as standardized mortality ratios (SMRs) with 95% confidence intervals (CIs). Results: There were 524 deaths during the follow-up period. PiZZ individuals had excess all-cause mortality compared with the Swedish general population (SMR 3.6, 95% CI 3.3&ndash;3.9). SMR for ischemic heart disease (IHD) was 0.5 (95% CI 0.3&ndash;0.8) and was similar for never and ever-smokers, and in males and females. SMR for lung cancer was 0.9 (95% CI 0.4&ndash;1.7). PiZZ individuals had increased mortality compared with the general population for the following diseases: respiratory disease, SMR 48.4 (95% CI 43.0&ndash;54.5); primary liver carcinoma, SMR 90.0 (95% CI 59.3&ndash;130.9); complicated colon diverticulitis, SMR 20.8 (95% CI 6.7&ndash;48.6); and pulmonary embolism, SMR 6.9 (95% CI 3.3&ndash;12.7). Conclusion: PiZZ individuals had a reduced mortality risk of IHD. Mortality due to respiratory, hepatic disease, diverticulitis, and pulmonary embolism was markedly increased compared with the age- and sex-matched Swedish population. Keywords: alpha 1-antitrypsin deficiency, cause-specific mortality, ischemic heart disease, pulmonary embolism, standardized mortality rati