Risk Factors For Lung Disease Research Articles

High-altitude Pulmonary Hypertension: an Update on Disease Pathogenesis and Management.

High-altitude pulmonary hypertension (HAPH) affects individuals residing at altitudes of 2,500 meters and higher. Numerous pathogenic variables play a role in disease inception and progression and include low oxygen concentration in inspired air, vasculopathy, and metabolic abnormalities. Since HAPH affects only some people living at high altitude genetic factors play a significant role in its pathogenesis. The clinical presentation of HAPH is nonspecific and includes fatigue, shortness of breath, cognitive deficits, cough, and in advanced cases hepatosplenomegaly and overt right-sided heart failure. A thorough history is important and should include a search for additional risk factors for lung disease and pulmonary hypertension (PH) such as smoking, indoor air pollution, left-sided cardiac disease and sleep disordered breathing. Twelve-lead electrocardiogram, chest X-ray and echocardiography can be used as screening tools. A definitive diagnosis should be made with right-sided heart catheterization using a modified mean pulmonary artery pressure of at least 30 mm Hg, differing from the 25 mm Hg used for other types of PH. Treatment of HAPH includes descent to a lower altitude whenever possible, oxygen therapy and the use of medications such as endothelin receptor antagonists, phosphodiesterase 5 blockers, fasudil and acetazolamide. Some recent evidence suggests that iron supplementation may also be beneficial. However, it is important to note that the scientific literature lacks long-term randomized controlled data on the pharmacologic treatment of HAPH. Thus, an individualized approach to treatment and informing the patients regarding the benefits and risks of the selected treatment regimen are essential.

A 63-year-old man with a recurrent right-sided pleural effusion

JPC : A 63-year-old Caucasian man was seen in clinic having been referred by his general practitioner with a 10 -week history of progressive exertional dyspnoea, associated with dry cough...

Risk factors for lung diseases after renal transplantation

Background:Lung diseases are one of the major causes of morbidity and mortality after renal transplantation. The aim of the study is to define the risk factors for infectious and noninfectious pulmonary complications in kidney transplant patients.Materials and Methods:We prospectively studied 267 patients after renal transplantation. The kidney recipients were followed-up for the development of pulmonary complications for a period of 7 years. Different noninvasive and invasive diagnostic tests were used in cases suspected of lung disease.Results:The risk factors associated with the development of pulmonary complications were diabetes mellitus (odds ratio [OR] = 4.60; P = 0.001), arterial hypertension (OR = 1.95; P = 0.015), living related donor (OR = 2.69; P = 0.004), therapy for acute graft rejection (OR = 2.06; P = 0.038), immunosuppressive regimens that includes mycophenolate (OR = 2.40; P = 0.011), azathioprine (OR = 2.25; P = 0.023), and tacrolimus (OR = 1.83; P = 0.041). The only factor associated with the lower risk of complications was a positive serology test for Cytomegalovirus of the recipient before transplantation (OR = 0.1412; P = 0.001).Conclusion:The risk factors can be used to identify patients at increased risk for posttransplant lung diseases. Monitoring of higher-risk patients allow timely diagnosis and early adequate treatment and can reduce the morbidity and mortality after renal transplantation.

Heredity of chronic bronchitis: A registry-based twin study

Smoking is a major risk factor for lung diseases and lower respiratory symptoms, but since not all smokers develop chronic bronchitis and since chronic bronchitis is also diagnosed in never-smokers, it has been suggested that some individuals are more susceptible to develop chronic bronchitis due to genetics. To study the relative influence of genetic and environmental factors on the variation in the susceptibility to chronic bronchitis. In a population-based questionnaire study of 13,649 twins, 50-71 years of age, from the Danish Twin Registry, we calculated sex-specific concordance rates and heritability of chronic bronchitis. The response rate was 75%. The prevalence of chronic bronchitis was 9.3% among men and 8.5% among women. The concordance rate for chronic bronchitis was higher in monozygotic twins than in dizygotic twins among women; 0.30 vs. 0.17, but not among men; 0.15 vs. 0.18. The heritability of chronic bronchitis adjusted for smoking and age was 55% (36-71%) in women, whereas the susceptibility to chronic bronchitis in men for 25% (8-41%) was ascribable to familial environment but not to genetic factors. Chronic bronchitis shows a moderate familial aggregation, particularly in women. Increased susceptibility to respiratory disease among female smokers relative to male smokers may have a genetic origin.

Identification of nuclear phosphoproteins as novel tobacco markers in mouse lung tissue following short-term exposure to tobacco smoke

Smoking is a risk factor for lung diseases, including chronic obstructive pulmonary disease and lung cancer. However, the molecular mechanisms mediating the progression of these diseases remain unclear. Therefore, we sought to identify signaling pathways activated by tobacco-smoke exposure, by analyzing nuclear phosphoprotein expression using phosphoproteomic analysis of lung tissue from mice exposed to tobacco smoke. Sixteen mice were exposed to tobacco smoke for 1 or 7days, and the expression of phosphorylated peptides was analyzed by mass spectrometry. A total of 253 phosphoproteins were identified, including FACT complex subunit SPT16 in the 1-day exposure group, keratin type 1 cytoskeletal 18 (K18), and adipocyte fatty acid-binding protein, in the 7-day exposure group, and peroxiredoxin-1 (OSF3) and spectrin β chain brain 1 (SPTBN1), in both groups. Semi-quantitative analysis of the identified phosphoproteins revealed that 33 proteins were significantly differentially expressed between the control and exposed groups. The identified phosphoproteins were classified according to their biological functions. We found that the identified proteins were related to inflammation, regeneration, repair, proliferation, differentiation, morphogenesis, and response to stress and nicotine. In conclusion, we identified proteins, including OSF3 and SPTBN1, as candidate tobacco smoke-exposure markers; our results provide insights into the mechanisms of tobacco smoke-induced diseases.

The burden of heart failure in Africa

Over the last few years, the focus of the international health community has shifted from communicable diseases as the main cause of morbidity and mortality in Africa (and indeed in the world in general) to non-communicable diseases. Relatively scant recent research suggests that in Africa cardiovascular (CV) diseases are a leading cause of morbidity and mortality, where up to 25% of admissions to hospitals are for CV disease, including hypertension (HTN). 14 Heart failure (HF) is the most common CV disorder and the main driver of CV adverse morbidity and mortality. 15 In this respect, the study by Ojji et al. in this month’s issue of the journal is a welcomed addition. In this hospital-based study, the authors report on the current spectrum of (CV) diseases in Abuja—the new and modern capital of the Federal Republic of Nigeria. The data from Abuja were compared with the findings in Soweto, a predominantly Black community in South Africa. The findings suggest that CV diseases in Abuja, Nigeria are mainly nonischaemic in origin and occur mainly in a younger and productive age group. Hypertension was found to be the most common cause, followed by dilated cardiomyopathies and rheumatic heart disease. The authors noted some subtle differences in the heart disease pattern in Abuja and Soweto. While there are higher rates of HTN and hypertensive HF in Abuja, ischaemic heart disease and right HF were more common in the Soweto study. As noted by the authors, this may be related to a higher burden of CAD and lung disease risk factors such as cigarette smoking, obesity, dyslipidaemia, and diabetes in Soweto compared with Abuja. Furthermore, peripartum cardiomyopathy is not as common a cause of CV disease and HF as expected. Given this relative lack of published data, putting the results of Ojji et al. into perspective is difficult. However, previous studies have found similar trends in different African countries and communities. 15 In most studies, HTN is followed by other disease entities that are less common outside of Africa, such as idiopathic dilated cardiomyopathy and rheumatic heart diseases. The Heart of Soweto registry from the Soweto township in South Africa, which is also described in the manuscript itself, found similar, although not identical trends (see above). In a registryof 2908 patients presenting for CV diseases to a clinic in Mzuzu central hospital in Malawi during a 5-year period, the most common causes of CV morbidity were rheumatic (34%), HTN (24%), cardiomyopathies (most commonly idiopathic dilated; 19%), and pericardial disease (14%). Atherosclerosis represented only 1–4% of cases. These trends are observed everywhere in Africa—in published and unpublished data, such as those depicted in a poster in the waiting area of a county hospital in Tzaneen; the Northern Province of South Africa (Figure 1). Indeed, similar results were published in studies from Nigeria 7 summarized in detail in the review by Ogah et al. These studies show that the prevalence of HTN in the general Nigerian population ranges from 8% to 46.4%. More importantly, it seems that the prevalence of HTN is increasing—from 8.6% reported in the only population-based study during the period from 1970 to 1979 to 22.55% during the period 2000–2011. HTN-related complications such as stroke, hypertensive heart disease (including hypertensive HF), andchronic kidneydisease is common andoften severe inhypertensive Nigerians. Late presentation is also common. Awareness, treatment, and control of HTN are low, as in many developing countries of the world. Regarding admissions for HF, in a smaller study from the Yaounde general hospital in Cameroon, the main causes of HF admissions were HTN (54%), cardiomyopathies (26%), and valvular heart diseases (24%). Ischaemic heart diseasewas the fifth most common aetiology (2.4%). In a registry of 1000 patients admitted for HF and followed prospectively by Damasceno et al., the most common causes of HF were HTN (45%) and rheumatic heart disease (14%), while ischaemic heart disease (8%) was not a common cause for HF. The study by Ojji et al., besides being one of the largest registries of CV diseases and HF in Africa, emphasizes two additional important aspects of CV diseases and HF and their treatment. First, the age of the patients affected is younger than in other world regions. Damasceno et al., Stewart et al., and Sliwa et al. have shown that CV diseases and HF occur in Africa at a younger age than outside Africa. In the series from Malawi, Soliman et al. found that the average age of patients presenting with CV diseases is as low as 40 years. Other studies describing CV admissions in Nigeria found the age of admission to be 50–55 years. 7,10 In the study of Ojji et al. the

Risk of Chronic Bronchitis in Twin Pairs Discordant for Smoking

It is well known that smoking is a major risk factor for lung disease and respiratory symptoms. We examined the association between smoking and the risk of chronic bronchitis in a large twin sample. In a population-based questionnaire study of 13,649 twins, aged 50-71years, from the Danish Twin Registry, we identified 1,146 twin pairs, discordant for a lifetime history smoking. We performed co-twin control analysis to examine the impact of smoking on the risk of chronic bronchitis. The prevalence of chronic bronchitis was 9.7%. In the total sample, high age, living without a spouse, and smoking remained statistically significant predictors with an up to tenfold increased risk of chronic bronchitis in the heaviest smokers compared with never-smokers, after multivariate adjustment. Among twin pairs discordant for smoking, chronic bronchitis was significantly more common in the smoking twin compared with the nonsmoking co-twin. There was no differential effect of smoking on the risk of chronic bronchitis in monozygotic and dizygotic twins. The risk of chronic bronchitis increases with age and increasing tobacco consumption. The results indicate a direct relationship between smoking and development of chronic bronchitis, but other environmental factors, such as exposure to household smoking in childhood and living without a spouse, also play a role.

High Levels of Anti-Cyclic Citrullinated Peptide Autoantibodies Are Associated with Co-occurrence of Pulmonary Diseases with Rheumatoid Arthritis

To investigate whether levels of anti-cyclic citrullinated peptide antibodies (anti-CCP2) in patients with rheumatoid arthritis (RA) are associated with the co-occurrence of lung diseases. A total of 252 RA patients were included in a cross-sectional study. Pulmonary disease was confirmed by high-resolution chest computed tomography scan. Circulating anti-CCP2 were quantified using ELISA. Multivariate logistic regression was conducted to identify independent risk factors for lung disease. Male sex (OR 3.29, 95% CI 1.59-6.80) and high anti-CCP2 levels (OR 1.49, 95% CI 1.25-1.78) were identified as independent risk factors for lung disease in the RA population. High anti-CCP2 levels are associated with lung disease in the RA population.

α1-Antitrypsin Augmentation Therapy for PI*MZ Heterozygotes: A Cautionary Note

The use of IV augmentation therapy with plasma-derived α₁-antitrypsin (AAT) has become the standard of care for the treatment of pulmonary disease associated with the severe genetic deficiency of AAT. The Medical and Scientific Advisory Committee of the Alpha-1 Foundation has become aware that physicians are prescribing this expensive blood product for the treatment of individuals with a single abnormal AAT gene, primarily the PI*MZ genotype. We are aware of no evidence that such therapy is effective in this patient population. The most important therapeutic interventions in such patients remain smoking cessation and elimination of other risk factors for lung disease. This commentary discusses the treatment of AAT deficiency and the concerns regarding treatment of PI*MZ individuals. We conclude that clinicians should avoid prescribing augmentation therapy for this heterozygote population.

Mannose-binding lectin polymorphisms and pulmonary outcome in premature neonates: a pilot study

Mannose-binding lectin (MBL2) is a collectin molecule able to activate the complement system and the subsequent inflammatory mechanisms. Several MBL2 genetic variants have been described, including the six variants studied in this report, which are those analyzed in most detail in the medical literature. The present study analyzes the prevalence of MBL2 gene variants in preterm newborns and associates individual genotypes with pulmonary outcome variables. All polymorphisms were analyzed by means of a commercially available reverse dot-blot kit. Tertiary neonatal intensive care unit. Seventy-five consecutive preterm newborns. Two variants were particularly analyzed: -550G > C and R52C. The first one is known to be associated with lower protein synthesis when included in specific haplotypes. The homozygous and heterozygous -550G > C mutations were significantly associated with protective effects regarding different lung outcome variables, including shorter duration of mechanical ventilation, hours of continuous positive airway pressure and lower number of hemotransfusions. In contrast, the heterozygous R52C mutation was associated with unfavorable outcome, including higher bronchopulmonary dysplasia prevalence. Multivariate logistic regression analysis showed that these associations were independent of gestational age and birth weight. In addition, four groups of patients were defined on the basis of haplotype combinations. Those known to be associated with low serum MBL2 levels were linked to a better outcome in terms of factors such as hours of mechanical ventilation, continuous positive airway pressure, number of hemotransfusions and bronchopulmonary disease development. The four haplotype combination groups may have a potential diagnostic use as opposite risk factors for lung disease of prematurity.

Cigarette smoking and khat chewing among university instructors in Ethiopia.

To assess the prevalence and risk factors of cigarette smoking and khat chewing. College based cross sectional. Four colleges found in north west Ethiopia namely Gondar College of Medical Sciences, Gondar College of Teachers Education, Bahr Dar University Engineering Faculty, and Bahr Dar University Education Faculty. All instructors in these colleges. Prevalence of cigarette smoking and khat chewing. Seventy six (42.0%) instructors were either lifetime smokers or lifetime khat chewers or both. The current prevalence rates of cigarette smoking and khat chewing were found to be 13.3% and 21.0%, respectively. The majority of the instructors started smoking (56.8%) and khat chewing (40.0%) while they were senior high school or first year college students. Most of the instructors (82.1%) knew that cigarette smoking is a risk factor for lung diseases including lung cancer. Statistically significant difference (p<0.05) was seen between the outcome variable and the independent variables faculty, religion, education status, income and family history of khat chewing. The prevalence of cigarette smoking seemed to decrease among university instructors but the prevalence of khat chewing is almost the same as it was some years ago. Instructors knew the common health risks associated with cigarette smoking. The high schools and colleges should inform their students about the health and socioeconomic problems associated with cigarette smoking and khat chewing. Additionally, college students need counseling service on ways of coping with their problems.

Occupational Inhalant Exposure and Respiratory Disorders among Never-Smokers Referred to a Hospital Pulmonary Function Laboratory

Multiple reports have described associations between occupational inhalant exposure and lung disease. Previous occupational lung disease investigations have studied populations consisting of both smokers and nonsmokers. Smoking complicates interpretation of toxicant exposure-response relationships. The objective of this study was to determine whether, among never-smokers, occupational exposure to gases, dusts, or fumes is associated with a history of respiratory disorders and pulmonary function test defined obstructive lung disease. We performed a retrospective analysis of 517 never-smoker patients who underwent pulmonary function testing in our clinical laboratory between 1986 and 1999. We calculated the relative risks of developing adverse respiratory health outcomes given a history of exposure to occupational inhalants. Compared with persons with a negative occupational exposure history, exposed persons had an increased risk of reporting a history of bronchitis [relative risk (RR), 1.59; 95% confidence interval (CI), 1.20-2.12], recurrent lung infections (RR, 2.09; 95% CI, 1.14-3.82), and bronchodilator use (RR, 1.61; 95% CI, 1.26-2.06). There was also a statistically significant association between a history of inhalant exposure and the finding of an obstructive ventilatory defect on pulmonary function testing (RR, 1.79; 95% CI, 1.12-2.85). A history of inhalant exposure was not associated with self-reported asthma (RR, 1.08; 95% CI, 0.83-1.41). The population attributable risk estimates for respiratory disorders due to inhalant exposure were: bronchitis, 23.6%; recurrent lung infection, 36.3%; bronchodilator use, 24.3%; and obstructive lung disease, 29.6%. Occupational inhalant exposure is a strong risk factor for lung disease in this population of never smokers. A significant burden of respiratory disease in this population may be attributable to occupational inhalant exposure.

Nicotine switches the form of H 2O 2-induced cell death from apoptosis to necrosis in U937 cells

Cigarette smoking is a major risk factor for lung diseases and oral diseases. The present study examined the effect of nicotine on H 2O 2-induced apoptosis in U937 cells. In the presence of 1 μg/ml nicotine, cell viability was not affected, but the cells were unable to undergo H 2O 2-induced apoptosis and instead died as a result of necrosis. Nicotine reduced the intracellular level of ATP, which is an important determinant of the form of cell death. These results suggest that nicotine can alter the cell death pathway by reducing the level of intracellular ATP, and that this effect may contribute to cigarette smoke-induced tissue destruction.

Occupational exposure to dust and lung disease among sheet metal workers.

A previous large medical survey of active and retired sheet metal workers with 20 or more years in the trade indicated an unexpectedly high prevalence of obstructive pulmonary disease among both smokers and non-smokers. This study utilised interviews with a cross section of the previously surveyed group to explore occupational risk factors for lung disease. Four hundred and seven workers were selected from the previously surveyed group on the basis of their potential for exposure to fibreglass and asbestos. Selection was independent of health state, and excluded welders. A detailed history of occupational exposure was obtained by telephone interview for 333 of these workers. Exposure data were analysed in relation to previously collected data on chronic bronchitis, obstructive lung disease, and personal characteristics. Assessment of the effects of exposure to fibreglass as distinct from the effects of exposure to asbestos has been difficult in previous studies of construction workers. The experienced workers studied here have performed a diversity of jobs involving exposure to many different types of materials, and this enabled exposure to each dust to be evaluated separately. The risk of chronic bronchitis increased sharply by pack-years of cigarettes smoked; current smokers had a double risk compared with those who had never smoked or had stopped smoking. The occurrence of chronic bronchitis also increased with increasing duration of exposure to asbestos. Workers with a history of high intensity exposure to fibreglass had a more than doubled risk of chronic bronchitis. Obstructive lung disease, defined by results of pulmonary function tests at the medical survey, was also related to both smoking and occupational risk factors. Number of pack years smoked was the strongest predictor of obstructive lung disease. Duration of direct and indirect exposure to welding fume was also a positive predictor of obstructive lung disease. Duration of exposure to asbestos was significantly associated with obstructive lung disease but the dose-response relation was inconsistent, especially for those with higher pack-years of smoking exposure. Exposure to fibreglass was not a risk factor for obstructive lung disease.

EFFECTS OF PRENTAL SMOKING ON LUNG FUNCTION IN INFANTS UNDER 4 MOTH OF AGE

Exposure to parental smoking has been associated with decreased lung function and respiratory symptoms in later life. Animals exposed to cigarette smoke have been reported to have altered lung volume compared to controls. We selected 87 infants <4 mo who were randomly enrolled in a prospective study of risk factors for lung disease. Maximal flows at FRC (Vmax FRC) were measured by the rapid chest compression technique, and FRC by helium-dilution. 20 infants' mothers smoked during the pregnancy (S) and 67 did not (NS). There were significantly (<.001) more smoking fathers in the S group. The prevalence of chronic respiratory problems in the family was the same in the both groups. Results are summarized in the table: These preliminary data suggest that infants born to smoking mothers show a tendency to have a larger lung parenchyma and lower volume-corrected flows. We speculate that dysnaptic growth patterns may occur in-utero, and are consistent with decreased flows, but larger lung volumes are observed in older children raised by smoking parents.