Atopy, lung function, and obstructive airways disease after prenatal exposure to famine

BACKGROUND: Associations have been found between a large head size at birth and atopy, and between low birth weight and obstructive airways disease. A study was undertaken of people born around the time of the Dutch famine in 1944-5 to determine the effects of maternal malnutrition during specific periods of gestation on the prevalence of obstructive airways disease and atopy. METHODS: Nine hundred and twelve people aged about 50, born at term between November 1943 and February 1947 in Amsterdam, were asked about their medical history. Lung function was measured in 733 and serum concentrations of total IgE and specific IgE against mite, pollen and cat were measured in 726. Those exposed in late, mid, and early gestation (exposed participants) were compared with those born before or conceived after the famine (non-exposed participants). RESULTS: Exposure to famine during gestation affected neither the concentrations of total or specific IgE nor lung function values. The prevalence of obstructive airways disease was increased in people exposed to famine in mid gestation (odds ratio adjusted for sex 1.7, 95% confidence interval (CI) 1.1 to 2.6) and tended to be higher in those exposed in early gestation (odds ratio 1.5, 95% CI 0. 9 to 2.6). CONCLUSIONS: The observed increase in the prevalence of obstructive airways disease in people exposed to famine in mid and early gestation was not parallelled by effects on IgE concentrations or lung function. The link between exposure to famine in mid and early gestation and obstructive airways disease in adulthood suggests that fetal lungs can be permanently affected by nutritional challenges during periods of rapid growth.     

Alterations in rat pancreatic B-cell function induced by prenatal exposure to cyproheptadine

Treatment of pregnant rats with cyproheptadine during the last 8 days of gestation produced alterations in the function of the endocrine pancreas in the offspring. The abnormalities exhibited by 50-day-old progeny of drug-treated dams included glucose intolerance, a two-fold increase in levels of insulin in the pancreas, and an accentuated response to the insulin-lowering action of cyproheptadine in the endocrine pancreas. The alterations observed in these animals were limited to the insulin-containing cells, and no change was found in the pancreatic concentrations of glucagon and somatostatin. The results are the first to demonstrate that postnatal pancreatic B-cell function can be selectively altered by prenatal exposure to an exogenous chemical.     

Changes in lung function after routine exposure manipulations during thoracotomy

The effect of manual retraction and bronchial occlusion upon right lung function during a 2-hr thoracotomy was evaluated in sheep. Group 1 (seven sheep) underwent manual lung retraction. Group 2 (seven sheep) underwent right bronchial occlusion. Group 3 (seven sheep) served as controls. Radioisotopic indicators (51Cr-RBC, 125I-albumin, [14C]urea, 3H2O) were used to assess changes in capillary permeability-surface area product (PS-urea), extravascular lung water (VE), and intravascular blood volume (Vv). Lung water was further quantified by gravimetric technique. Pulmonary vascular resistance increased following thoracotomy in both groups (34% Group 1, 66% Group 2) and compliance decreased (16% Group 1, 33% Group 2). Mean right lung shunt increased in Group 1 from 17 to 37% (P less than 0.05) and for Group 2 from 18 to 36% (P less than 0.02). A reduction (greater than 25%) in both groups for PS-urea and VE occurred (P less than 0.05). The fall in PS-urea and VE and the increase in PVR indicate a reduction in the right lung perfusion for both groups. It is concluded that a similar marked reduction in ventilation, perfusion, and V/Q occurred after reexpansion whether the lung was retracted or the bronchus occluded.     

Pulmonary function in adult survivors of severe acute lung injury treated with inhaled nitric oxide

Background : Following an episode of acute respiratory distress syndrome (ARDS), some degree of measurable pulmonary impairment may be anticipated. ARDS is thought to be the more severe form of acute lung injury (ALI) and a recently proposed addition to conventional therapy in ALI/ARDS is inhaled nitric oxide (INO). We carried out a non-randomised follow-up study with pulmonary function tests on survivors of severe ALI/ARDS treated with INO.
Methods : Sixteen previously healthy pulmonary patients, survivors of severe ALI/ARDS, were evaluated with pulmonary function tests >8 months after the acute event. The tests included static and dynamic spirometry, diffusion capacity for carbon monoxide (DLCO), blood gas analysis and evaluation of a chest radiograph.
Results : The most common abnormality seen was a low DLCO in 69% of the patients. Abnormally low values were seen in forced vital capacity in 31%, in forced expiratory volume in 1 s in 13%, and in residual volume and total lung capacity in 6%. Blood gas data were within normal limits in 15/16 patients. All chest radiographs showed resolution of the interstitial and alveolar changes present during the acute event.
Conclusion : In this non-randomised follow-up study we conclude that a degree of measurable pulmonary impairment after INO treatment in severe ALI/ARDS was common, but did not differ markedly from other published studies on pulmonary function in similar patient material. No late unexpected major abnormalities due to the inhaled nitric oxide treatment could be identified in these survivors.     

Relation of fetal growth to adult lung function in south India

BACKGROUND: Follow up studies in Britain have shown that low rates of fetal growth are followed by reduced lung function in adult life, independent of smoking and social class. It is suggested that fetal adaptations to undernutrition in utero result in permanent changes in lung structure, which in turn lead to chronic airflow obstruction. India has high rates of intrauterine growth retardation, but no study has examined the association between fetal growth and adult lung function in Indian people. We have related size at birth to lung function in an urban Indian population aged 38-59 years. METHODS: Two hundred and eighty six men and women born in one hospital in Mysore City, South India, during 1934-1953 were traced by a house-to-house survey of the city. Their mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured using a turbine spirometer. These measurements were linked to their size at birth, recorded at the time. RESULTS: In both men and women mean FEV1 fell with decreasing birthweight. Adjusted for age and height, it fell by 0.09 litres with each pound (454 g) decrease in birthweight in men (95% confidence interval (CI) 0.01 to 0.16) and by 0.06 (95% CI -0.01 to 0.13) in women. Likewise, mean FVC fell by 0.11 litres (95% CI 0.02 to 0.19) with each pound decrease in birthweight in men, and by 0.08 litres (95% CI 0.002 to 0.16) in women. FEV1 and FVC were lower in men who smoked, but the associations with size at birth were independent of smoking. Small head circumference at birth was associated with a low FEV1/FVC ratio in men which may reflect restriction in airway growth in early gestation. CONCLUSION: This is further evidence that adult lung function is "programmed" in fetal life. Smoking may be particularly detrimental to the lung function of populations already disadvantaged by poor rates of fetal growth.


     

Cumulative exposure to CD8+ granzyme Bhi T cells is associated with reduced lung function early after lung transplantation

Outcomes following lung transplant remain suboptimal. This is attributable to variable posttransplant recovery of lung function, and inconsistent degrees of lung function loss after peak function is reached. Granzyme B is elevated in the blood and bronchoalveolar lavage (BAL) in acute rejection. We hypothesized that persistent exposure to T cells high in granzyme B would negatively correlate with lung function. We investigated cumulative exposure measured as the area-under-the-curve (AUC) of CD8⁺ T cell granzyme B^hi cells in the first year posttransplant in both BAL and blood in 24 transplant recipients. We assessed the correlation between cumulative 1-year exposure and FEV₁ slope. There was a negative correlation between 1-year exposure and FEV₁ slope within the first year (r = −0.63; P = .001). This relationship persisted even when adjusted for transplant type, gender, age, rejection, and indication for transplantation. In contrast, no relationship was seen with the 1-year AUC and lung function after 1 year posttransplant. In contrast to the BAL granzyme B^hi levels, granzyme B^hi levels from the blood showed no relationship with lung function. These findings suggest that CD8⁺ T-cell–driven factors are responsible for early improvements in lung function after transplantation.     

Influence of prenatal waterpipe tobacco smoke exposure on reproductive hormones and oxidative stress of adult male offspring rats

Male infertility is adversely affected by tobacco cigarette smoking. Herein, the effects of prenatal waterpipe tobacco smoke (WTS) exposure on reproductive hormones and oxidative stress of adult offspring rats were evaluated. Pregnant rats received either fresh air or mainstream WTS (2 hr daily). Pregnancy outcomes, circulatory levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin, testicular levels of oestrogen, testosterone and oxidative stress biomarkers [catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS)] were assessed in their adult male offspring rats. Prenatal WTS exposure reduced the number of born offspring, female to pups ratio and birthweight (p < 0.05). Prenatal WTS exposure increased the circulatory levels of FSH and the testicular levels of oestrogen, testosterone and TBARS and catalase activity compared with control group (p < 0.05). However, GPx activity was reduced by WTS exposure (p < 0.05). There appeared to be a trend of increased LH and prolactin levels with prenatal WTS exposure; however, it was not statistically significant compared with control group (p > 0.05). The activity of SOD was not affected by prenatal WTS exposure (p > 0.05). In conclusion, prenatal WTS exposure altered reproductive hormones as well as oxidative stress biomarkers in adult male offspring rats.     

Long-term acceptance of renal allografts following prenatal inoculation with adult bone marrow

BACKGROUND: The aim was to investigate if intravascular in utero injection of adult bone marrow into swine fetuses could lead to macrochimerism and tolerance to the donor. METHODS: Outbred Yorkshire sows and boars screening negative for MHC allele SLA of MGH miniature swine were bred. A laparotomy was performed on the sows at 50 days gestation to expose the uterus. Bone marrow harvested from SLA miniature swine was T-cell depleted and injected intravascularly into seventeen fetuses. Flow cytometry was performed to detect donor cells (chimerism) in the peripheral blood after birth. Mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML) assays were used to assess the response to donor MHC. Previously frozen skin grafts from the bone marrow donor were placed on the offspring from the first litter. Donor-matched renal transplant from SLA donors were performed on chimeric swine, with and without a short 12-day course of cyclosporine, and one nonchimeric littermate. RESULTS: Nine inoculated offspring demonstrated donor cell chimerism in the peripheral blood and lymphohematopoietic tissues. All animals with detectable chimerism within the first three weeks were consistently nonreactive to donor MHC in vitro. Animals challenged with donor skin grafts displayed prolonged graft survival without producing antidonor antibodies. All chimeric animals accepted donor-matched kidney allografts, even one without cyclosporine. The kidney in the nonchimeric littermate rejected by day 21. CONCLUSIONS: Transplantation of allogeneic adult bone marrow into immunocompetent fetal recipients resulted in chimerism. In utero inoculation led to operational tolerance to the donor's major histocompatibility antigens and long-term acceptance to organ allografts.     

Assessment of thyroid function with hormone assays

Measurement of serum thyroid hormone and TSH levels provide diagnostic information in the majority of patients with thyroid dysfunction. The test strategy in hyperthyroidism differs from that in hypothyroidism. Serum T4 is a good test for hyperthyroidism in patients with normal thyroid hormone-binding protein levels. When binding proteins are abnormal serum free T4 is a much more accurate test for hyperthyroidism than serum T4. Serum T3 and the TSH response to TRH are useful tests for the early diagnosis of hyperthyroidism. Serum TSH is a very sensitive indicator of primary hypothyroidism rising already at the subclinical stage of the disease. Serum T4 and free T4, but not serum T3, are useful for the verification of clinical hypothyroidism. Determination of the TRH-stimulated TSH level is important for the differential diagnosis of pituitary and hypothalamic hypothyroidism. It is imperative to recognize that thyroid tests are often abnormal in various non-thyroidal diseases and that administration of drugs can affect these tests. Serum rT3 is of some value for the assessment of thyroid function in patients with non-thyroidal disease.     

Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function

BACKGROUND: Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development. METHODS: A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students in 1993. Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics. RESULTS: In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (-3.0%, 95% CI -4.4 to -1.4), mean mid expiratory flow (MMEF) (-4.6%, 95% CI -7.0 to -2.3), and forced expiratory flow (FEF(75)) (-6.2%, 95% CI -9.1 to -3.1), but not forced expiratory volume in one second (FEV(1)). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (-4.1%, 95% CI -7.6 to -0. 4) and FEF(75) (-4.4%, 95% CI -9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF(75) associated with all measurements of ETS were substantially reduced and were not statistically significant. CONCLUSIONS: In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows.     

Relationship between birth weight and adult lung function: controlling for maternal factors

BACKGROUND: There is conflicting evidence on the "fetal origins hypothesis" of association between birth weight and adult lung function. This may be due to failure to control for confounding maternal factors influencing birth weight. In the present study access to birth details for adults aged 45-50 years who were documented as children to have asthma, wheezy bronchitis, or no respiratory symptoms provided an opportunity to investigate this association, controlling for maternal factors. METHODS: In 2001 the cohort was assessed for current lung function, smoking status, and respiratory symptoms. Birth details obtained from the Aberdeen Maternity and Neonatal Databank recorded birth weight, gestation, parity, and mother's age and height. RESULTS: 381 subjects aged 45-50 years were traced and tested for lung function; 323 (85%) had birth details available. A significant linear trend (p<0.01) was observed between birth weight and current forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) values (adjusted for height, age, sex, weight, deprivation category (Depcat), childhood group, and smoking status). This trend remained significant after adjusting birth weight for gestation, parity, sex, mother's height and weight (p = 0.01). The relationship between birth weight and FEV(1) and FVC remained significant when adjusted for smoking history. There was no association between birth weight and current wheezing symptoms. CONCLUSION: There is a positive linear trend between birth weight, adjusted for maternal factors, and lung function in adulthood. The strength of this association supports the "fetal origins hypothesis" that impairment of fetal growth is a significant influence on adult lung function.     

Birth weight, childhood lower respiratory tract infection, and adult lung function

BACKGROUND—Historicalcohort studies in England have found that impaired fetal growth andlower respiratory tract infections in early childhood are associatedwith lower levels of lung function in late adult life. These relationsare investigated in a similar study in Scotland.
METHODS—In 1985-86 afollow up study was carried out of 1070 children who had been born inSt Andrew's from 1921 to 1935 and followed from birth to 14 years ofage by the Mackenzie Institute for Medical Research. Recordedinformation included birth weight and respiratory illnesses. The lungfunction of 239 of these individuals was measured.
RESULTS—There was noassociation between birth weight and lung function. Pneumonia beforetwo years of age was associated with a difference in mean forcedexpiratory volume in one second (FEV₁) of −0.39 litres(95% confidence interval (CI) −0.67,−0.11; p = 0.007) and in mean forced vitalcapacity (FVC) of −0.60 litres (95% CI −0.92, −0.28; p<0.001),after controlling for age, sex, height, smoking, type of spirometer,and other illnesses before two years. Similar reductions were seen inmen and women. Bronchitis before two years was associated with smallerdeficits in FEV₁ and FVC. Asthma or wheeze at two years andolder and cough after five years were also associated with a reductionin FEV₁.
CONCLUSIONS—Therelation between impaired fetal growth and lower lung function in lateadult life seen in previous studies was not confirmed in this cohort.The deficits in FEV₁ and FVC associated with pneumonia andbronchitis in the first two years of life are consistent with a causal relation.

     

Traffic exposure and lung function in adults: the Atherosclerosis Risk in Communities study

BACKGROUND: Traffic exposure is a major contributor to ambient air pollution for people living close to busy roads. The relationship between traffic exposure and lung function remains inconclusive in adults. METHODS: A cross-sectional study was conducted to investigate the association between traffic exposure and lung function in the Atherosclerosis Risk in Communities (ARIC) study, a community based cohort of 15 792 middle aged men and women. Traffic density and distance to major roads were used as measures of traffic exposure. RESULTS: After controlling for potential confounders including demographic factors, personal and neighbourhood level socioeconomic characteristics, cigarette smoking and background air pollution, higher traffic density was significantly associated with lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in women. Relative to the lowest quartile of traffic density, the adjusted differences across increasing quartiles were 5.1, -15.4 and -21.5 ml for FEV1 (p value of linear trend across the quartiles = 0.041) and 1.2, -23.4 and -34.8 ml for FVC (p trend = 0.010). Using distance from major roads as a simpler index of traffic related air pollution exposure, the FEV1 was -15.7 ml (95% CI -34.4 to 2.9) lower and the FVC was -24.2 ml (95% CI -46.2 to -2.3) lower for women living within 150 m compared with subjects living further away. There was no significant effect of traffic density or distance to major roads on lung function in men. The FEV1/FVC ratio was not significantly associated with traffic exposure in either men or women. CONCLUSIONS: This is the largest published study of traffic exposure and pulmonary function in adults to date. These results add to growing evidence that chronic exposure to traffic related air pollution may adversely affect respiratory health.     

Effects of exposure to a mobile phone on testicular function and structure in adult rabbit

The accumulating effects of exposure to electromagnetic radiation emitted by a conventional mobile phone (standby position) on the testicular function and structure are not yet fully investigated. To study these effects longitudinally, a total of 24 adult male rabbits were randomly and equally divided into three groups. Rabbits in the first (phone) group were exposed, in specially designed cages, to radio frequency emitted from the mobile phone (800 MHz) in a standby position opposite to that of testes for 8 h daily for 12 weeks. The second group consisted of the stress controls which were kept in the same kind of cages to appreciate any cage-induced anxiety. The third group included the ordinary controls which were kept in the conventional roomy cages. Semen analysis and sperm function tests (viability, hypo-osmotic swelling and acridine orange) were conducted weekly. Histological testicular sections and serum total testosterone were also evaluated. A drop in the sperm concentration appeared in the phone group at week 6. This became statistically significant at week 8, compared with the two control (stress and ordinary) groups (133, 339 and 356 × 106/mL, respectively) and to the initial sperm count (341 × 106/mL) of this group. Motile sperm population showed similarity amongst the three study groups until week 10 when it declined significantly, and thereafter in the phone and stress control groups, with more significant decline in the phone animals (50, 61 and 72.4%, respectively). Histological examination showed also a significant decrease in the diameter of seminiferous tubules in the phone group vs. the stress and ordinary controls (191 μm vs. 206 and 226 μm, respectively). The other study points did not show any difference. In conclusion, low intensity pulsed radio frequency emitted by a conventional mobile phone kept in the standby position could affect the testicular function and structure in the adult rabbit.     

术前肺功能参数预测低肺功能患者肺癌根治术后并发呼吸衰竭的评价

目的对拟行肺癌根治术的低肺功能患者进行常规肺功能检测和脉冲强迫振荡技术（IOS）检测，评价术前肺功能参数预测低肺功能患者肺癌根治术后并发呼吸衰竭的价值。方法按照常规肺功能评价标准和术前肺功能测定结果，选择52例拟行肺癌根治术、低肺功能患者，根据术后是否发生呼吸衰竭分为呼衰组和非呼衰组。术前检测常规肺功能参数：第1秒用力呼气容积（FEV1．0）、肺活量（VC）及最大通气量（MVV）；IOS检测参数：周边气道阻力（R5-R20）、弹性阻力（X5）、共振频律（Fres）。结果两组FEV1．0、R5-R50、X5、Fres差异有统计学意义（P〈0．05）；Logisfic回归分析显示仅Fres为预测术后呼吸衰竭发生的独立因素（P〈0．01）。结论Fres有助于预测低肺功能肺癌患者全肺切除术后是否发生呼吸衰竭。