| 1. |
- Basil, Nawfal, et al.
(författare)
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Severe alpha-1-antitrypsin deficiency increases the risk of venous thromboembolism
- 2021
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Ingår i: Journal of Thrombosis and Haemostasis. - : John Wiley & Sons. - 1538-7933 .- 1538-7836. ; 19:6, s. 1519-1525
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is associated with increased risk of liver disease and chronic obstructive pulmonary disease (COPD), but the risk of venous thromboembolism (VTE) is unknown. Our aim was to evaluate the risk of VTE in individuals with severe AATD compared with control subjects from the general population.Methods: Individuals with severe AATD (n = 1577) were recruited from the Swedish national AATD register. Control subjects (n = 5969) were selected from the OLIN (Obstructive Lung Disease in Northern Sweden) studies, that include a random general population sample. Longitudinal data on VTE and diagnoses were obtained from the Swedish National Patient Registry. Associations were analyzed using multivariable Cox regression.Results: At inclusion, 46% of the AATD individuals and 53% of the controls were never-smokers. COPD was present in 46% of the AATD individuals compared with 4% of the controls. During a median follow-up of 18 years, 116 (7%) of the AATD individuals and 89 (1%) of the control subjects developed VTE, unadjusted hazard ratio 6.5 (95% confidence interval 4.9–8.6). Risk factors for incident VTE were male gender, age, COPD, cancer, and liver disease. Adjusting for these factors, the AATD individuals had a significantly higher risk of incident VTE, adjusted hazard ratio 4.2 (95% confidence interval 2.9–6.2) as compared with the controls.Conclusion: Subjects with severe AATD have considerably increased risk of developing VTE compared with the general population, even after accounting for risk factors. This calls for optimized risk factor management and clinical follow-up of this patient group.
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| 2. |
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| 3. |
- Ekström, Magnus, et al.
(författare)
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Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.
- 2024
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Ingår i: Respiratory research. - : BioMed Central (BMC). - 1465-993X .- 1465-9921. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population.Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64years. Breathlessness (modified Medical Research Council [mMRC]≥2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease.We included 25,948 people aged 57.5±[SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI≥30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers.Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.
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| 4. |
- Ekström, Magnus, et al.
(författare)
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Lung transplantation and survival outcomes in patients with oxygen-dependent COPD with regard to their alpha-1 antitrypsin deficiency status
- 2017
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Ingår i: International Journal of COPD. - 1176-9106. ; 12, s. 3281-3287
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Tidskriftsartikel (refereegranskat)abstract
- Background: Individuals with severe alpha-1 antitrypsin deficiency (AATD) have an increased risk of developing COPD. However, outcomes during long-term oxygen therapy (LTOT) in patients with severe AATD and hypoxemia are unknown. Patients and methods: This was a prospective, population-based, consecutive cohort study of patients on LTOT due to COPD in the period from January 1, 1987, to June 30, 2015, in the Swedish National Registry for Respiratory Failure (Swedevox). Severe AATD was identified using the Swedish AATD registry and confirmed by isoelectric focusing. Data on lung transplantation (LTx) were obtained from the two lung transplantation centers in Sweden. Mortality and causes of death were assessed based on the National Causes of Death Registry and analyzed using multivariable Cox regression. Results: A total of 14,644 patients who started LTOT due to COPD were included in this study. No patient was lost to follow up. Patients with AATD were younger, included more males and more never smokers, and had fewer comorbidities. During a median follow-up of 1.6 years (interquartile range [IQR], 2.7) on LTOT, patients without severe AATD had a higher mortality, hazard ratio [HR] 1.53 (95% CI, 1.24–1.88), adjusting for age, sex, smoking status, body mass index, performance status, level of hypoxemia, and comorbidities. Cardiovascular deaths were increased. A higher proportion of AATD patients underwent LTx, 53 (19%) vs 118 (1%). Survival after LTx was similar for AATD and non-AATD patients and was predicted by age. Conclusion: In oxygen-dependent COPD, patients with severe AATD have a longer survival time on LTOT, but they have a similar prognosis after lung transplantation compared with patients without AATD.
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| 5. |
- Ekström, Magnus Pär, et al.
(författare)
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The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study
- 2019
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
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| 6. |
- Ekström, Magnus, et al.
(författare)
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Risk of cancer after lung transplantation for COPD
- 2017
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Ingår i: International Journal of COPD. - 1176-9106. ; 12, s. 2841-2847
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Tidskriftsartikel (refereegranskat)abstract
- 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-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<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.
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| 7. |
- Genberg, Jenny, et al.
(författare)
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Indications and patterns of use of benzodiazepines and opioids in severe interstitial lung disease : a population based longitudinal study
- 2021
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite evidence that opioids might relieve chronic breathlessness, physicians may still be reluctant to prescribe them due to safety concerns. By contrast, benzodiazepine (BDZ) prescribing often seeks to reduce chronic breathlessness despite no evidence of net benefit. Prescribing patterns and indications for these medications in severe interstitial lung disease (ILD) are unknown. Here, our objective was to evaluate the indications, medications and temporal patterns of BDZ and opioid prescriptions in people with oxygen-dependent ILD.Methods: This was an observational, population-based, longitudinal study of adults starting long-term oxygen therapy (LTOT) for ILD between 2005 and 2014 in the Swedish National Registry for Respiratory Failure (Swedevox). People dispensed BDZs (n=2000) and opioids (n=2000) from 6 months before start of LTOT throughout follow-up (first of death or study end) were analysed.Results: Of 1635 included patients, 651 (39.8%) received BDZs and 710 (43.4%) received opioids during the study period; 373 (22.8%) patients received both. The most frequently prescribed BDZs and opioids were oxazepam (85.6%) and oxycodone (28.7%), respectively. Indications for breathlessness were uncommon for BDZs (1.4%) and opioids (6.4%). During the last year of life, opioid indications for breathlessness increased from 2.5% (12-10 months before death) to 10.2% in the last 3 months of life (p=0.048).Conclusions: In oxygen-dependent ILD, opioids are rarely prescribed for breathlessness even in the last months of life, when chronic breathlessness often increases in prevalence and intensity.
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| 8. |
- Hiller, Adriana Maria, et al.
(författare)
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Cancer risk in severe alpha-1-antitrypsin deficiency
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 60:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is a risk factor for pulmonary emphysema and liver disease, but its effect on cancer risk is unknown. Our aim was to evaluate the risk and the risk factors for incident cancer in PiZZ individuals compared with the general population with known smoking habits.METHODS: A longitudinal study of PiZZ individuals (n=1595) from the Swedish National AATD Register, and controls (n=5999) from Swedish population-based cohorts. Data on cancer and mortality were obtained by cross-linkage with national registers. Individuals who had undergone lung transplantation (n=10) and those with a cancer diagnosis within 5 years prior to inclusion (n=63) were excluded. The risk factors for developing cancer were analysed using proportional hazards and Fine-Gray regression models, adjusting for age, sex, smoking habits and the presence of liver disease.RESULTS: The median follow-up time was 17 years (interquartile range 11 years) for the whole study population. The incidence rates of hepatic and non-hepatic cancer per 1000 person-years were 1.6 (95% CI 1.1-2.3) and 8.5 (95% CI 7.2-10.0), respectively, for the PiZZ individuals, and 0.1 (95% CI 0.04-0.2) and 6.6 (95% CI 6.0-7.1), respectively, for the controls. The adjusted hazard ratios for hepatic and for non-hepatic cancer were 23.4 (95% CI 9.9-55.4) and 1.3 (95% CI 1.1-1.5), respectively, in the PiZZ individuals compared with the controls.CONCLUSION: These results suggest that individuals with severe AATD may have an increased risk of developing both hepatic and non-hepatic cancer, compared with the general population.
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| 9. |
- Hiller, Adriana Maria, et al.
(författare)
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Cancer risk in severe alpha-1-antitrypsin deficiency: the importance of early identification
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 60:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is a risk factor for pulmonary emphysema and liver disease, but its effect on cancer risk is unknown. Our aim was to evaluate the risk and the risk factors for incident cancer in PiZZ individuals compared with the general population with known smoking habits. Methods A longitudinal study of PiZZ individuals (n=1,595) from the Swedish National AATD Register, and controls (n=5,999) from Swedish population-based cohorts. Data on cancer and mortality were obtained by cross-linkage with national registers. Individuals who had undergone lung transplantation (n=10) and those with a cancer diagnosis within five years prior to inclusion (n=63) were excluded. The risk factors for developing cancer were analyzed using proportional hazards and Fine-Gray regression models, adjusting for age, sex, smoking habits and the presence of liver disease. Results The median follow-up time was 17 years (IQR 11) for the whole study population. The incidence rate of hepatic and non-hepatic cancer per 1,000 person-years was 1.6 (95% CI 1.1-2.3) and 8.5 (95% CI 7.2-10.0) for the PiZZ individuals, and 0.1 (95% CI 0.04-0.2) and 6.6 (95% CI 6.0-7.1) for the controls, respectively. The adjusted hazard ratios (HR) for hepatic and for non-hepatic cancer were 23.4 (95% CI 9.9-55.4) and 1.3 (95% CI 1.1-1.5) respectively, in the PiZZ individuals compared with the controls. Conclusion These results suggest that individuals with severe alpha-1-antitrypsin deficiency may have an increased risk of developing both hepatic and non-hepatic cancer, compared with the general population.
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| 10. |
- Hiller, Adriana-Maria, et al.
(författare)
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Decline in FEV1 and hospitalized exacerbations in individuals with severe alpha-1 antitrypsin deficiency
- 2019
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Ingår i: International Journal of COPD. - 1178-2005. ; 14, s. 1075-1083
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: The value of the forced expiratory volume in one second (FEV1) is useful in the diagnosis and prognosis of chronic obstructive pulmonary disease (COPD). Previous studies on lung function in individuals with severe alpha-1 antitrypsin deficiency (AATD) have shown a variable annual decline in FEV1 (∆FEV1). The aim of this study was to analyze ∆FEV1 and to identify risk factors for ∆FEV1 in individuals with severe AATD.Material and methods: Data on smoking habits, symptoms, results of lung function tests and exacerbations were obtained from the Swedish AATD Register and the Swedish National Patient Register (SNPR). The ∆FEV1 was analyzed by random-effects modeling and adjusted for age and FEV1 at baseline.Results: One hundred and four (9%) current smokers, 539 (48%) ex-smokers and 489 (43%) never-smokers were included in the study and followed-up from 1991 to 2016. A total of 584 (52%) individuals with severe AATD had COPD at inclusion. The median (IQR) annual severe exacerbation rate was 0.66 (1.4). The adjusted mean ∆FEV1 was significantly higher in the current smokers compared with the ex-smokers and never-smokers (70 [95% CI 56–83] vs 42 [95% CI 36–48] and 32 [95% CI 25–38) mL·yr−1,], in the middle–aged individuals compared with the young individuals (48 [95% CI 41–55] vs 32 [95% CI 18–45] mL·yr−1,), in the individuals with respiratory symptoms at inclusion compared with the asymptomatic individuals (46 [95% CI 40–52] vs 30 [95% CI 22–38]mL·yr−1,), and in the individuals with frequent exacerbations compared with those with infrequent exacerbations (57 [95% CI 47–68] vs 27 [95% CI 17–37] mL·yr−1,).Conclusion: Active smoking, age, respiratory symptoms at baseline and repeated severe exacerbations of COPD are factors associated with an accelerated decline of lung function in individuals with severe AATD.
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| 11. |
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| 12. |
- Hiller, Adriana Maria, et al.
(författare)
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The Clinical Course of Severe Alpha-1-Antitrypsin Deficiency in Patients Identified by Screening
- 2022
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Ingår i: International journal of chronic obstructive pulmonary disease. - 1178-2005. ; 17, s. 43-52
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe alpha-1-antitrypsin deficiency (AATD) is a genetic condition predisposing to chronic obstructive pulmonary disease (COPD) and liver disease. Its natural course is not well known. Our aim was to study the natural course of AATD by analyzing the clinical course in individuals with severe AATD identified by screening.Materials and Methods: Of the 1585 individuals included in the Swedish AATD register, 377 (24%) were identified by screening and included in this retrospective study. The follow-up time was from the date of inclusion in the register to the first lung transplantation, death or the termination of the study on June 1st, 2016. The risk factors for having a diagnosis of COPD were investigated through a proportional hazards model, adjusted for sex, diagnosis before the age of 14 years, smoking habits, occupational exposure to airway irritants and respiratory symptoms or diseases.Results: At inclusion, 71% of the individuals were asymptomatic, ie, without any respiratory symptoms. Compared to the 156 (41%) ever-smokers, the 221 (59%) never-smokers had better lung function (mean FEV1 98 (SD 18) vs 85 (SD 28) % predicted; p < 0.001), and fewer of them were symptomatic, ie, with respiratory symptoms, at inclusion (20% vs 42%; p < 0.001). They also had a lower annual decline in FEV1 (mean 42 (95% CI 36-47) vs 53 (95% CI 47-60) mL·yr-1; p = 0.011) and better survival than the ever-smokers. The risk factors for having a diagnosis of COPD were the identification of severe AATD at an age of ≥14 years and the presence of respiratory symptoms or diseases.Conclusion: Never-smoking individuals with severe AATD identified by screening have better lung function, fewer symptoms, and better survival compared with the ever-smokers. Screening for AATD at an early age may improve the prognosis of AATD.
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| 13. |
- Malinovschi, Andrei, 1978-, et al.
(författare)
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Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry
- 2023
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:4, s. 461-471
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Post-bronchodilator (BD) spirometry is used for diagnosis of chronic obstructive pulmonary disease (COPD). However, pre-BD reference values are used for spirometry interpretation.OBJECTIVES: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or post-BD reference values generated within the Swedish CArdioPulmonary bioImage Study (SCAPIS) when interpreting post-BD spirometry in a general population.METHODS: SCAPIS reference values for post-BD and pre-BD spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or post-BD reference values, with respiratory burden in the SCAPIS general population (28,851 individuals).MEASUREMENTS AND MAIN RESULTS: Bronchodilation resulted in higher predicted median and lower limit of normal (LLN) for FEV1/FVC ratio. The prevalence of post-BD FEV1/FVC < pre-bronchodilator LLN was 4.8% and that of post-BD FEV1/FVC < post-bronchodilator LLN was 9.9% for the general population. An additional 5.1% was identified as having an abnormal post-BD FEV1/FVC ratio and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%, p<0.001) and self-reported physician-diagnosed COPD (2.8% vs. 0.5%, p<0.001) than subjects with post-BD FEV1/FVC ratio > LLN for both pre- and post-bronchodilation).CONCLUSIONS: Pre- and post-bronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of post-bronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using post-bronchodilator reference values when interpreting post-bronchodilator spirometry might enable identification of individuals with mild disease and be clinically relevant.
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| 14. |
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| 15. |
- Miravitlles, Marc, et al.
(författare)
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Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency : EARCO international registry
- 2022
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. Results: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). Conclusions: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registrationwww.clinicaltrials.gov
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| 16. |
- Mostafavi, Behrouz, et al.
(författare)
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Liver function in alpha-1-antitrypsin deficient individuals at 37 to 40 years of age
- 2017
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Ingår i: Medicine. - 0025-7974 .- 1536-5964. ; 96:12
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Tidskriftsartikel (refereegranskat)abstract
- Severe alpha-1-antitrypsin (AAT) deficiency (PiZZ) is a risk factor for liver disease, but the prevalence of liver cirrhosis and hepatocellular cancer in PiZZ adults is unknown. The risk of liver disease in adults with moderate AAT deficiency (PiSZ) is also unknown. A cohort of 127 PiZZ, 2 PiZnull, 54 PiSZ, and 1 PiSnull individuals were identified by the Swedish national neonatal AAT screening program between 1972 and 1974, when all 200, 000 newborn infants in Sweden were screened for AAT deficiency. The cohort has been followed up since birth. Our aim was to study liver function and signs of liver disease in this cohort at 37 to 40 years of age in comparison with a matched, random sample of control subjects identified from the population registry. Eighty seven PiZZ, 32 PiSZ, and 92 control subjects (PiMM) answered a questionnaire on medication and alcohol consumption and provided blood samples. Liver stiffness was assessed by Acoustic Radiation Force Impulse (ARFI) elastography in 32 PiZZ, 15 PiSZ, and 51 PiMM subjects. The median of liver function tests and procollagen-III-peptide were within the normal range in all Pi subgroups. However, the PiZZ men had significantly higher plasma bilirubin than the PiMM men (P=0.018). Plasma ?-glutamyl transferase (GGT) was significantly higher in the PiZZ men (P=0.009) and the PiSZ men (P=0.021) compared with the PiMM men. The median of liver stiffness was significantly higher in the PiZZ men (P=0.037) and the PiSZ men (P=0.032) compared with the PiMM men. The PiZZ women taking medication influencing liver enzymes had significantly higher GGT than the PiMM women on the corresponding treatment (P=0.023). These AAT-deficient individuals identified by neonatal screening have normal plasma levels of liver function tests, and no clinical signs indicating liver disease at the age of 37 to 40 years. However, bilirubin, GGT, and liver stiffness are significantly higher in PiZZ men than PiMM men.
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| 17. |
- Mostafavi, Behrouz, et al.
(författare)
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Lung function and CT lung densitometry in 37-to 39-year-old individuals with alpha-1-antitrypsin deficiency
- 2018
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Ingår i: International Journal of COPD. - 1176-9106. ; 13, s. 3689-3698
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alpha-1-antitrypsin (AAT) deficiency is a hereditary disorder that predisposes to emphysema. A cohort of severe (PiZZ) and moderate (PiSZ) AAT-deficient newborn infants was identified by the Swedish national neonatal AAT screening program in 1972–1974 and has been followed-up since birth. Our aim was to study whether the cohort has signs of emphysema in pulmonary function tests (PFTs) and computed tomography (CT) densitometry at 38 years of age in comparison with an age-matched control group, randomly selected from the population registry. Methods: Forty-one PiZZ, 18 PiSZ, and 61 control subjects (PiMM) underwent complete PFTs, measurement of resistance and reactance in the respiratory system by impulse oscillometry (IOS)/forced oscillation technique (FOT), and CT densitometry. The results were related to self-reported smoking habits. Results: The total lung capacity (TLC) % of the predicted value was significantly higher in the PiZZ ever-smokers than in the PiZZ never-smokers (P<0.05), PiSZ never-smokers (P=0.01) and the PiMM never-smokers (P=0.01). The residual volume (RV) % of the predicted value was significantly higher in the PiZZ ever-smokers compared to the PiMM never-smokers (P<0.01). The PiZZ ever-smokers had a significantly lower carbon monoxide transfer coefficient (Kco) than the PiSZ never-smokers (P<0.01) and PiMM never-smokers (P<0.01). Respiratory system resistance at 5 Hz (P<0.01), at 20 Hz (P<0.01), and the area of low reactance (Alx; P<0.05) were significantly lower and respiratory system reactance at 5 Hz (P<0.05) was significantly higher in PiZZ subjects compared to the PiMM subjects. No statistically significant differences in the CT densitometry parameters were found between the Pi subgroups. Conclusion: The physiological parameters in the PiZZ ever-smokers showed evidence of hyperinflation and emphysema before the age of 40 years.
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| 18. |
- Mostafavi, Behrouz, et al.
(författare)
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Survival in the Swedish cohort with alpha-1-antitrypsin deficiency, up to the age of 43-45 years
- 2019
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Ingår i: International Journal of COPD. - 1176-9106. ; 14, s. 525-530
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Tidskriftsartikel (refereegranskat)abstract
- 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 1972-1974 and has been followed up since birth. Our aim was to study survival in this cohort up to 43-45 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 1972-1974, 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 0.77-3.94). Four PiSZ subjects died compared to an expected 1.53 deaths, giving an SMR of 2.61 (95% CI 0.71-6.71). The cumulative probability of survival up to the age of 45 years was 94% (95% CI 90%-98%) for the study population. Six deaths occurred before the age of 8 years. Conclusion: Up to 43-45 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.
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| 19. |
- Nygren, David, et al.
(författare)
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Low Prevalence of Mild Alpha-1-Antitrypsin Deficiency in Hospitalized COVID-19-Patients
- 2022
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Ingår i: International Journal of General Medicine. - : Dove Medical Press Ltd. - 1178-7074. ; 15, s. 5843-5848
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Alpha- 1-antitrypsin (AAT) has been shown to inhibit SARS-CoV-2 cell entry and suggested as a therapeutic agent for COVID-19. Furthermore, epidemiological association of high prevalence of Alpha- 1-antitrypsin deficiency (AATD) and regional severity of COVID-19-impact has been hypothesized. In our study setting, the estimated prevalence rates of mild (PI*MZ, PI*SS or PI*MS) and moderate-to-severe AATD (PI*ZZ or PI*SZ) are high, 9% and 0.2%, respectively. Our primary aim was to examine the prevalence rate of AATD among hospitalized COVID-19-patients. Methods: In this prospective observational study, enrollment occurred from December 2020 to January 2021 in two COVID-19-units at Skane University Hospital, Lund, Sweden. Case definition was a patient hospitalized due to COVID-19. Patients were screened for AATD with PI-typing and if results were inconclusive, PCR for the S- and Z-genes were performed. Patients were categorized as severe or moderate COVID-19 and 30-day-mortality data were collected. The primary outcome was prevalence rate of AATD. The secondary outcome investigated association between presence of mild AATD and severe COVID-19. Results: We enrolled 61 patients with COVID-19. Two patients out of 61 (3%) had mild AATD (PI*MZ) and none had moderate-tosevere AATD. 30/61 (49%) had severe COVID-19. Both patients with mild AATD developed severe COVID-19. Yet, presence of AATD was not significantly associated with severe COVID-19 (p=0.24). Conclusion: Mild AATD (PI*MS or PI*MZ) was rare in a small cohort of hospitalized patients with COVID-19 in a study setting with a high background prevalence of AATD.
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| 20. |
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| 21. |
- Pesonen, Ida, et al.
(författare)
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High prevalence of interstitial lung abnormalities in middle-aged never-smokers
- 2023
-
Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms.METHODS: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing.FINDINGS: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA.INTERPRETATION: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.
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| 22. |
- Piitulainen, Eeva, et al.
(författare)
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Health status and lung function in the Swedish alpha 1-antitrypsin deficient cohort, identified by neonatal screening, at the age of 37-40 years
- 2017
-
Ingår i: International Journal of COPD. - 1176-9106. ; 12, s. 495-500
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Tidskriftsartikel (refereegranskat)abstract
- 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 1972-1974 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 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<0.001), symptom score (P<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 <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.
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| 23. |
- Piitulainen, Eeva, et al.
(författare)
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Lung Function and CT Densitometry in Subjects with alpha-1-Antitrypsin Deficiency and Healthy Controls at 35 Years of Age.
- 2015
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Ingår i: COPD: Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1541-2563 .- 1541-2555. ; 12:2, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Alpha-1-antitrypsin (AAT) deficiency is a genetic risk factor for pulmonary emphysema. In 1972-74 all 200,000 Swedish new-born infants were screened for AAT deficiency. The aim of the present study was to investigate whether the PiZZ and PiSZ individuals identified by this screening have signs of emphysema and the role of smoking in this, compared with a random sample of control subjects at 35 years of age. The study participants underwent complete pulmonary function tests (PFT) and CT densitometry. The fifteenth percentile density (PD15) and the relative area below -910 HU (RA-910) were analyzed. Fifty-four PiZZ, 21 PiSZ and 66 PiMM control subjects participated in the study. No significant differences were found in lung function between the never-smoking AAT-deficient and control subjects. The 16 PiZZ ever-smokers had significantly lower carbon monoxide transfer coefficient (KCO) than the 20 PiSZ never-smokers (p = 0.014) and the 44 PiMM never-smokers (p = 0.005). After correction for the CT derived lung volume, the PiZZ ever-smokers had significantly lower PD15 (p = 0.046) than the ever-smoking controls. We conclude that 35-year-old PiZZ and PiSZ never-smokers have normal lung function when compared with never-smoking control subjects. The differences in KCO and CT densitometric parameters between the PiZZ ever-smokers and the control subjects may indicate early signs of emphysema.
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| 24. |
- Piitulainen, Eeva, et al.
(författare)
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The Clinical Profile of Subjects Included in the Swedish National Register on Individuals with Severe Alpha 1-Antitrypsin deficiency.
- 2015
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Ingår i: COPD: Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1541-2563 .- 1541-2555. ; 12, s. 36-41
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish national register of severe alpha1-antitrypsin (AAT) deficiency was established in 1991. The main aims are to prospectively study the natural history of severe AAT deficiency, and to improve the knowledge of AAT deficiency. The inclusion criteria in the register are age ≥18 years, and the PiZ phenotype diagnosed by isoelectric focusing. The register is kept updated by means of repeated questionnaires providing data to allow analysis of the mode of identification, lung and liver function, smoking-habits, respiratory symptoms and diagnoses as reported by physicians. Until February 2014, a total of 1553 PiZZ individuals had been included in the register. The 1102 subjects still alive constituted about 20% of the adult PiZZ individuals in Sweden. Forty-three percent of the subjects had been identified during investigation of respiratory symptoms, 7% by an investigation of liver disease, 26% in an investigation of other pathological conditions, and 24% in a population or family screening. Forty five percent of the subjects had never smoked, 47% were ex-smokers, and 8% current smokers. Twenty-eight percent of the never-smokers, 72% of the ex-smokers, and 61% of the current smokers fulfilled the criteria for COPD with a FEV1/FVC ratio of <0.70. Among the 451 deceased, the most common cause of death was respiratory diseases (55%), followed by liver diseases (13%). We conclude that the detection rate of severe AAT deficiency is relatively high in Sweden. Large numbers of subjects are identified for other reasons than respiratory symptoms, and the majority of these have never smoked.
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| 25. |
- Schramm, Georg Rüdiger, et al.
(författare)
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Lung Function and Health Status in Individuals with Severe Alpha-1-Antitrypsin Deficiency at the Age of 42
- 2021
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Ingår i: International Journal of COPD. - 1176-9106. ; 16, s. 3477-3485
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe hereditary alpha-1-antitrypsin deficiency (AATD) is a known risk factor for the early development of pulmonary emphysema and COPD, especially in smo-kers. By the Swedish national screening programme carried out from 1972 to 1974, a cohort of individuals with severe (PiZZ) AATD was identified and has been followed up regularly. The aim of this study was to investigate health status, quality of life and lung function in this cohort at the age of 42 years compared with an age-matched control group randomly selected from the population registry. Methods: All study participants answered a questionnaire on smoking habits, symptoms, occupation, exposure to airway irritants and quality of life using Saint George’s Respiratory Questionnaire (SGRQ). They underwent complete pulmonary function tests (PFT) and forced oscillation technique (FOT) for the measurement of airway resistance and reactance. Blood samples were taken for allergies and IgG-subclasses as an indicator of increased risk of airway infections. Results: The residual volume (RV), total lung capacity (TLC) and RV/TLC ratio were significantly higher in the PiZZ ever-smokers compared to the PiMM ever-smokers and PiZZ never-smokers (p < 0.05). The resistance in the upper, small and total airways was significantly lower in PiZZ subjects compared to PiMM subjects (p < 0.05). A greater propor-tion of PiZZ never-smokers had an FEV1 /VC ratio <0.7 than PiMM never-smokers (p = 0.043). PiZZ subjects with occupational exposure to airway irritants showed a significantly lower FEV1, VC and higher RV/TLC ratio than PiMM individuals with exposure (p < 0.05). Conclusion: At the age of 42, ever-smoking PiZZ individuals have signs of COPD, and also PiZZ never-smokers have early, physiological signs of emphysema.
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| 26. |
- Sundh, Josefin, 1972-, et al.
(författare)
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Advanced Dental Cleaning is Associated with Reduced Risk of COPD Exacerbations : A Randomized Controlled Trial
- 2021
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : Dove Medical Press Ltd.. - 1176-9106 .- 1178-2005. ; 16, s. 3203-3215
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Infections from the oral microbiome may lead to exacerbations of chronic obstructive pulmonary disease (COPD). We investigated whether advanced dental cleaning could reduce exacerbation frequency. Secondary outcomes were disease-specific health status, lung function, and whether the bacterial load and composition of plaque microbiome at baseline were associated with a difference in outcomes.Patients and Methods: One-hundred-one primary and secondary care patients with COPD were randomized to intervention with advanced dental cleaning or to dental examination only, repeated after six months. At baseline and at 12 months, data of exacerbations, lung function, COPD Assessment Test (CAT) score, and periodontal status were collected from questionnaires, record review, and periodontal examination. Student's t-test and Mann-Whitney-U (MWU) test compared changes in outcomes. The primary outcome variable was also assessed using multivariable linear regression with adjustment for potential confounders. Microbiome analyses of plaque samples taken at baseline were performed using Wilcoxon signed ranks tests for calculation of alpha diversity, per mutational multivariate analysis of variance for beta diversity, and receiver operating characteristic curves for prediction of outcomes based on machine learning models.Results: In the MWU test, the annual exacerbation frequency was significantly reduced in patients previously experiencing frequent exacerbations (p = 0.020) and in those with repeated advanced dental cleaning (p = 0.039) compared with the non-treated control group, but not in the total population including both patients with a single and repeated visits (p = 0.207). The result was confirmed in multivariable linear regression, where the risk of new exacerbations was significantly lower in patients both in the intention to treat analysis (regression coefficient 0.36 (95% CI 0.25-0.52), p < 0.0001) and in the population with repeated dental cleaning (0.16 (0.10-0.27), p < 0.0001). The composition of microbiome at baseline was moderately predictive of an increased risk of worsened health status at 12 months (AUC = 0.723).Conclusion: Advanced dental cleaning is associated with a reduced frequency of COPD exacerbations. Regular periodontal examination and dental cleaning may be of clinical importance to prevent COPD exacerbations.
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| 27. |
- Tanash, Hanan A., et al.
(författare)
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Burn injury during long-term oxygen therapy in Denmark and Sweden : the potential role of smoking
- 2017
-
Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - 1176-9106 .- 1178-2005. ; 12, s. 193-197
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Tidskriftsartikel (refereegranskat)abstract
- 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 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], 126-225) vs 85 (95% CI, 44-148) per 100,000 person-years; rate ratio 2.0 (95% CI, 1.0-4.1). 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.
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| 28. |
- Tanash, Hanan A., et al.
(författare)
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Cause-specific mortality in individuals with severe alpha 1-antitrypsin deficiency in comparison with the general population in Sweden
- 2016
-
Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - 1176-9106 .- 1178-2005. ; 11, s. 1663-1669
-
Tidskriftsartikel (refereegranskat)abstract
- 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 3.3-3.9). SMR for ischemic heart disease (IHD) was 0.5 (95% CI 0.3-0.8) and was similar for never and ever-smokers, and in males and females. SMR for lung cancer was 0.9 (95% CI 0.4-1.7). PiZZ individuals had increased mortality compared with the general population for the following diseases: respiratory disease, SMR 48.4 (95% CI 43.0-54.5); primary liver carcinoma, SMR 90.0 (95% CI 59.3-130.9); complicated colon diverticulitis, SMR 20.8 (95% CI 6.7-48.6); and pulmonary embolism, SMR 6.9 (95% CI 3.3-12.7). 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.
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| 29. |
- Tanash, Hanan A., et al.
(författare)
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Liver disease in adults with severe alpha-1-antitrypsin deficiency
- 2019
-
Ingår i: Journal of Gastroenterology. - : Springer Science and Business Media LLC. - 0944-1174 .- 1435-5922. ; 54:6, s. 541-548
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Tidskriftsartikel (refereegranskat)abstract
- Background: The proportion of adults with liver disease due to severe alpha-1-antitrypsin deficiency (AATD), with PiZZ phenotype, is not clear. The markers of the AATD liver disease, how it progresses, and measures for its prevention have not been established. The aim of this study was to analyze the risk of liver disease in individuals with severe AAT deficiency (PiZZ). Methods: Longitudinal clinical and laboratory data were obtained from the Swedish National registers, by cross-linkage between the Swedish national AATD register, the Swedish National Patient Register, the National Cancer Register and the National Causes of Death Register. Results: A total of 1595 PiZZ individuals were included in the analyses. The mean follow-up time was 12 years (range 0.3–24). The mean number of follow-ups was 5 (range 2–15). Two or more liver function tests (LFTs) were available in 1123 individuals, and 26% of them (n = 290) had repeated elevated LFTs during the follow-up. The prevalence of any liver disease was 10% (n = 155). Liver cirrhosis was found in 7% of the individuals (n = 116) and hepatocellular carcinoma in 2% (n = 29). The mean age at the onset of liver disease was 61 (SD 15) years. In multivariate analyses, the male gender, age over 50 years, repeated elevated LFTs, hepatitis virus infection, and a diagnosis of diabetes were associated with increased risk of developing liver disease in adulthood (p < 0.01). Conclusion: The prevalence of liver disease in adult PiZZ individuals is 10%. Age over 50 years, the male gender, repeated elevated liver enzymes, hepatitis, and the presence of diabetes mellitus are risk factors for developing liver disease.
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| 30. |
- Tanash, Hanan A., et al.
(författare)
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Survival in individuals with severe alpha 1-antitrypsin deficiency (PiZZ) in comparison to a general population with known smoking habits
- 2017
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 50:3
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about the natural history of severe alpha 1-antitrypsin (AAT) deficiency (PiZZ) is limited. Our aim was to compare the survival of PiZZ individuals with randomly selected controls from the Swedish general population. The PiZZ subjects (n=1585) were selected from the Swedish National AATD Register. The controls (n=5999) were randomly selected from the Swedish population register. Smoking habits were known for all subjects. Median follow-up times for the PiZZ subjects (731 never-smokers) and controls (3179 never-smokers) were 12 and 17 years, respectively (p<0.001). During follow-up, 473 PiZZ subjects (30%), and 747 controls (12%) died. The PiZZ subjects had a significantly shorter survival time than the controls, p<0.001. After adjustment for gender, age, smoking habits and presence of respiratory symptoms, the risk of death was still significantly higher for the PiZZ individuals than for the controls, hazard ratio (HR) 3.2 (95% CI 2.8-3.6; p<0.001). By contrast, the risk of death was not increased in never-smoking PiZZ individuals identified by screening, compared to never-smoking controls, HR 1.2 (95% CI 0.6-2.2). The never-smoking PiZZ individuals identified by screening had a similar life expectancy to the neversmokers in the Swedish general population. Early diagnosis of AAT deficiency is of utmost importance.
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| 31. |
- Tanash, Hanan
(författare)
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Clinical course and prognosis of individuals with severe alpha 1-antitrypsin deficiency (PiZZ)
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Severe alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with increases risk of developing of chronic obstructive lung disease and liver disease. The Swedish National Registry for individuals with severe AATD was started 1991.Up to October 2008, a total of 1349 individuals were included in the registry. The aims of the studies in this thesis which bases on AATD registry are to analyse the mortality of PiZZ individuals with respect to smoking habits and mode of identification, to analyse the predictors of mortality and to analyse the most common causes of death, by including a large number of never-smoking individuals. Further aims were to assess whether there is a survival benefit of lung transplantation in PiZZ individuals with severe emphysema. In study I and II, the PiZZ individuals had a significantly increased mortality risk compared with general Swedish population. We found that the smokers had a significantly higher mortality rate than the never-smokers and than the general population. The never-smoking individuals identified by screening did not have an increased mortality risk compared with the general population. Emphysema is still the main underlying cause of death in smoker-and never-smokers. Liver cirrhosis-related mortality seems to be increased in elderly never-smoking individuals, cirrhosis and its complications were the cause of death in 26 of 93 never-smokers. Increasing age, decreasing FEV1 % of predicted value and presence of respiratory symptoms were associated with increased mortality risk in PiZZ individuals. Study III shows a significant survival benefit for lung transplantation in PiZZ individuals with severe emphysema, with an estimated median survival time of 11 years compared to 7 years in the non-transplant patients. Furthermore, in Sweden, patients seem to be referred to the lung transplantation centers late in the disease which may result in an unnecessarily increased mortality for this group of patients. In study IV we did not find any significant differences in age, gender or smoking habits between the index and non-index siblings. Neither was there any significant difference in lung function at inclusion. Our study population was young in both groups with a mean age of 40 years or younger and the majority of both them were identified by screening.
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| 32. |
- Tanash, Hanan, et al.
(författare)
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Clinical course and prognosis of never-smokers with severe alpha-1-antitrypsin deficiency (PiZZ).
- 2008
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 63, s. 1091-1095
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies of non-smoking individuals with severe alpha-1-antitrypsin deficiency (PiZZ) have been sparse and included only a limited number of individuals, mostly identified by respiratory symptoms. The aim of this study was to estimate the prognosis of non-smoking PiZZ individuals and to analyze the most common causes of death by including a large number of individuals who had been identified due to reasons other than respiratory symptoms. METHODS: The study included 568 non-smoking PiZZ subjects who were selected from the Swedish National AAT Deficiency Registry and followed-up from 1991 to September 2007. Of these, 156 (27%) were identified by respiratory symptoms (respiratory cases) and 412 were identified by extra pulmonary symptoms or screening (non-respiratory cases). RESULTS: Ninety-three subjects (16%) died during the follow-up time. The specific Standardized Mortality Rate (SMR) for the whole study population was 2.32 (95% confidence interval (CI) 1.87-2.83) with no significant difference between men and women. The SMR was 2.55 (95% CI 1.91-2.83) for the respiratory cases and 2.07 (95% CI 1.49-2.81) for the non-respiratory cases. Further calculation of SMR for subgroups in the non-respiratory cases showed that the SMR was 0.70 (95% CI 0.14-2.04) for individuals identified by family/population screening. Emphysema and liver cirrhosis were the most common causes of death (45% and 28%, respectively). Malignant transformation was found in 38% of the cirrhotic cases. CONCLUSION: Non-smoking PiZZ individuals identified by screening do not have an increased mortality risk compared with the Swedish general population.
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| 33. |
- Tanash, Hanan, et al.
(författare)
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Decreased risk of ischemic heart disease in individuals with severe alpha 1-antitrypsin deficiency (PiZZ) in comparison with the general population
- 2020
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Ingår i: International Journal of COPD. - : Dove Medical Press Ltd.. - 1176-9106 .- 1178-2005. ; 15, s. 1245-1252
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe alpha-1-antitrypsin deficiency (AATD) is an established risk factor for chronic obstructive pulmonary disease (COPD) and liver disease, but the effect on the incidence of ischemic heart disease (IHD) is not well known. The aim was to evaluate the risk of incident IHD in patients with severe AATD compared with a random sample of the general population, with known smoking habits. Methods: AAT-deficient individuals, phenotype PiZZ (n=1545), were included in the Swedish National AATD Register. Controls (n=5883) were selected from population-based cohorts in Northern Sweden. Data on IHD and comorbidities were obtained by nationwide cross-linkage with the Swedish National Patient Register. Risk factors for incident IHD were analyzed using Cox regression, adjusted for age, gender, smoking status and the presence of COPD, hypertension, hyperlipidemia and diabetes. Results: At inclusion, 46% of the PiZZ individuals and 53% of the controls were neversmokers. During follow-up (median 16 years; range 0.2–23), 8% (n=123) of PiZZ individuals and 12% (n=690) of controls developed IHD. The controls had a significantly higher risk for incident IHD than the PiZZ individuals, with adjusted hazard ratio (HR) of 1.8 (95% CI 1.4–2.3). The risk was higher for controls in both ever-smokers (HR 2.1; 95% CI 1.5–2.9) and never-smokers (HR 1.5; 95% CI 1.1–2.2). Conclusion: PiZZ individuals have a lower risk of developing incident ischemic heart disease than the control subjects with known smoking habits, who had been randomly selected from population-based cohorts.
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| 34. |
- Tanash, Hanan, et al.
(författare)
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Survival benefit of lung transplantation for chronic obstructive pulmonary disease in sweden.
- 2014
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 98:6, s. 1930-1935
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Tidskriftsartikel (refereegranskat)abstract
- Lung transplantation (LTx) is a therapeutic option for patients with life-threatening chronic obstructive pulmonary disease (COPD) that is refractory to conventional therapies. The survival benefit of LTx for COPD is difficult to assess. The aim of this study was to evaluate the Swedish series of LTx performed to treat COPD and to identify differences in outcome between COPD related to severe alpha-1-antitrypsin deficiency (AATD) and COPD with normal alpha-1-antitrypsin (AAT) levels.
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| 35. |
- Tanash, Hanan, et al.
(författare)
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Survival benefit of lung transplantation in individuals with severe α(1)-anti-trypsin deficiency (PiZZ) and emphysema.
- 2011
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 30:12, s. 1342-1347
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objective of lung transplantation (LTx) is to prolong life, but the survival benefit for patients with severe α(1)-anti-trypsin deficiency (PiZZ) and emphysema is still unclear. The aim of this study was to assess whether PiZZ patients who have undergone lung transplantation (the lung transplant group, TxG) do better than patients who have continued on the usual medical therapy (the non-transplant group, NTxG). METHODS: Between 1990, when the first patient received a lung transplant in Sweden, until June 2010, a total of 83 PiZZ patients with severe emphysema underwent transplantation. Seventy appropriate controls were identified from the Swedish National AAT Deficiency Registry. Each control was matched with a patient who had received a lung transplant, for age, gender, smoking history (number of pack-years) and lung function at the time of transplantation. RESULTS: Both controls and lung transplant patients had low spirometric values with a mean FEV(1) of 23 ± 6% and 22 ± 9% of predicted value, respectively (not a statistically significant difference). Of the 83 transplant patients, 62 (75%) underwent single-lung transplantation (SLTx). During follow-up, 37 (45%) deaths occurred in the TxG and 45 (64%) in the NTxG. In the TxG, the estimated median survival time was 11 years (95% confidence interval [CI] 9 to 14 years), compared with 8 years (95% CI 4 to 6 years) for the NTxG (p = 0.006). The most common cause of death was pulmonary infection among the transplant patients (38%) and respiratory failure (60%) among the controls. CONCLUSION: Lung transplantation significantly improves long-term survival of patients with severe α(1)-anti-trypsin deficiency (PiZZ) and emphysema.
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| 36. |
- Tanash, Hanan, et al.
(författare)
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Survival in severe alpha-1-antitrypsin deficiency (PiZZ)
- 2010
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: 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. Methods: 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. Results: 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). Conclusion: Smokers with severe AAT deficiency, irrespective of mode of identification, have a significantly higher mortality risk than the general Swedish population.
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| 37. |
- Tanash, Hanan, et al.
(författare)
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The risk of burn injury during long-term oxygen therapy : a 17-year longitudinal national study in Sweden
- 2015
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - 1176-9106 .- 1178-2005. ; 10, s. 2479-2484
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Tidskriftsartikel (refereegranskat)abstract
- Background: 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 +/- 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, 0.55-3.1). 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, 36-98) 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.
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| 38. |
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| 39. |
- Torén, Kjell, 1952, et al.
(författare)
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The ratio FEV1/FVC and its association to respiratory symptoms-A Swedish general population study
- 2021
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:2, s. 181-191
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Tidskriftsartikel (refereegranskat)abstract
- Chronic airflow limitation (CAL) can be defined as fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) any respiratory symptom. In a cross-sectional general population study, 15,128 adults (50-64 years of age), 7,120 never-smokers and 8,008 ever-smokers completed a respiratory questionnaire and performed FEV1 and FVC after bronchodilation. We calculated different ratios of FEV1/FVC from 0.40 to 1.0 using 0.70 as reference category. We analysed odds ratios (OR) between different ratios and any respiratory symptom using adjusted multivariable logistic regression. Among all subjects, regardless of smoking habits, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.82, OR 0.48 (95% CI 0.41-0.56). Among never-smokers, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.81, OR 0.53 (95% CI 0.41-0.70). Among ever-smokers, the odds for any respiratory symptom was lowest at FEV1/FVC = 0.81, OR 0.43 (95% CI 0.16-1.19), although the rate of inclining in odds was small in the upper part, that is FEV1/FVC = 0.85 showed similar odds, OR 0.45 (95% CI 0.38-0.55). We concluded that the odds for any respiratory symptoms continuously decreased with higher FEV1/FVC ratios and reached a minimum around 0.80-0.85, with similar results among never-smokers. These results indicate that the optimal threshold associated with respiratory symptoms may be higher than 0.70 and this should be further investigated in prospective longitudinal studies.
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| 40. |
- Zaigham, Suneela, et al.
(författare)
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Triglyceride-Glucose Index is a Risk Marker of Incident COPD Events in Women
- 2022
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Ingår i: International journal of chronic obstructive pulmonary disease. - 1178-2005. ; 17, s. 1393-1401
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The triglyceride-glucose index (TyG index) is a marker of insulin resistance and metabolic dysfunction and has the advantage of being universally available. Although recent evidence suggests the TyG index has relevance to respiratory health, there have been no prospective studies assessing its value as a biomarker for chronic lung diseases. We aim to assess the TyG index as a potential risk marker for future incident COPD events in the general population.Patients and Methods: Baseline TyG index was assessed in 28,282 middle-aged men and women without previous history of chronic obstructive pulmonary disease (COPD) from the Malmö Preventive Project (men between 1974 and 1982 and women between 1982 and 1992). All subjects were followed up prospectively, and Cox proportional hazards regression was used to assess incident COPD events according to quartiles of TyG index.Results: After an average of 31 years of follow-up, TyG index was a strong predictor of future COPD events even after adjusting for potential confounders (Q4 (highest TyG index) HR (95% CI): 1.21 (1.09-1.35) vs Q1 (reference), p-trend <0.001). After stratifying by sex, the results remained statistically significant in women only (Q4 vs Q1 HR 1.72 (1.41-2.09)). Additionally, the risk remained significant in a cohort of life-long never smokers (Q4 vs Q1 HR 1.47 (1.08-2.01)).Conclusion: A raised TyG index is a novel risk marker of future incident COPD events in women. Insulin resistance as reflected by the TyG index can precede the development of obstructive lung disease and as such may be an easily measurable and useful predictor of COPD in women.
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