Respiratory Abstracts 3

© 2013

Pulmonary function measures as predictors and correlates of cognitive functioning in later life

            (Chyou, White et al. 1996) Download

The relation between pulmonary function and cognitive functioning was investigated in a cohort of 3,036 Japanese-American men living in Hawaii. Pulmonary function, as indicated by forced expiratory volume in 1 second (FEV1), was measured at the baseline examination from 1965 to 1968. Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI) test at least 23 years later (1991-1993). Baseline FEV1 was significantly correlated with follow-up CASI score (r = 0.22, p = 0.0001). Although the strength of the association was reduced by controlling for the effects of other factors, stepwise multiple linear regression showed that FEV1 during middle age was a significant predictor of CASI in later life, after taking into account the effects of age, education, stroke, sedentary job activity, nonmanual occupation, height, generation, and Japanese speaking ability. The mean CASI value was significantly greater for men whose FEV1 exceeded 2.8 liter compared with those whose FEV1 levels were in the lowest (<2.5 liters) quartile. Furthermore, the test on the effect of interaction between FEV1 and age was statistically significant (p = 0.0024), with subjects less than 55 years of age at the baseline examination showing a stronger direct association of FEV1 with CASI than the men aged 55 or older. These findings suggest that pulmonary function impairment may be associated with cognitive function impairment in later life.

Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease

            (Duvoix, Dickens et al. 2012) Download

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality. The most widely used marker of disease severity and progression is FEV(1). However, FEV(1) correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD. Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD. Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker. METHODS: Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV(1), cardiovascular disease, exacerbation and mortality. RESULTS: There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality. Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity. The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear. Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations. CONCLUSIONS: Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality.

The interaction of ageing and lung disease

         (Dyer 2012) Download

This article explores the structural and physiological changes that occur in the ageing lung, and the impact that lung disease and other co-morbidities may have on it. The major changes associated with ageing are reduced lung elasticity, respiratory muscle strength and chest wall compliance, all of which may be influenced by impaired lung growth in early childhood and adolescence. The resultant reduction in diffusing capacity may not be relevant in a fit older adult, but co-morbidities may interact to cause breathlessness and impairments in quality of life. Lung function declines with age, but forced vital capacity (FVC) begins to decline later than forced expiratory volume in 1 s (FEV(1)) and at a slower rate. This results in a natural fall in the FEV(1)/forced vital capacity (FVC) ratio which may result in overdiagnosis of chronic obstructive pulmonary disease, and hence the need to ensure the FEV(1) is less than 80% before confirming the diagnosis. As older adults probably have a diminished response to hypoxia and hypercapnia, they become more vulnerable to ventilatory failure during high-demand states such as heart failure and pneumonia and therefore to possible poorer outcomes. Poor nutritional status is likely to be an important factor, as is cognitive impairment. It is important to assess older patients using a range of clinical and physiological parameters rather than on the basis of age per se which is a poor predictor of outcome.


Apolipoprotein E genotype modifies the association between midlife lung function and cognitive function in old age

            (Giltay, Nissinen et al. 2009) Download

BACKGROUND/AIMS: Because poor lung function may be a risk factor for cognitive decline, we aimed to test the association of respiratory function with cognitive function and dementia later in life, as well as potential effect modification by APOE epsilon4 carrier status. METHODS: In a prospective population-based cohort study, forced vital capacity and forced expiratory flow were measured around 1965 in 857 men aged 45-64 years (394 from Finland, 208 from The Netherlands, and 255 from Italy). The Mini-Mental State Examination scores around 1990, 1995 and 2000 were analyzed using multilevel regression models and the Clinical Dementia Rating score around 1990 using multinomial logistic regression analyses. RESULTS: Midlife lung function was positively associated with cognitive function in old age in APOE epsilon4 non-carriers, but not in carriers (p < 0.05 for interaction). In Finland and Italy, 18.6% had questionable to mild dementia and 2.8% moderate to severe dementia after 25 years of follow-up. Dementia was inversely related to midlife lung function in APOE epsilon4 non-carriers, but not in carriers (p < 0.05 for interaction). CONCLUSIONS: Small lung volumes were prospectively associated with an increased risk for poor cognitive function and dementia in non-carriers of the APOE epsilon4 gene.

Histamine airway hyper-responsiveness and mortality from chronic obstructive pulmonary disease: a cohort study

            (Hospers, Postma et al. 2000) Download

BACKGROUND: Smoking and airway lability, which is expressed by histamine airway hyper-responsiveness, are known risk factors for development of respiratory symptoms. Smoking is also associated with increased mortality risks. We studied whether airway hyper-responsiveness is associated with increased mortality, and whether this risk was independent of smoking and reduced lung function. METHODS: We followed up 2008 inhabitants of the communities of Vlagtwedde, Vlaardingen, and Meppel (Netherlands), who had histamine challenge test data, from 1964-72 for 30 years. Follow-up was 99% successful (29 patients lost to follow-up) with 1453 participants alive and 526 deaths (246 died from cardiovascular disease, 54 from lung cancer, and 21 from chronic obstructive pulmonary disease [COPD]). FINDINGS: Mortality from COPD increased with more severe hyper-responsiveness; relative risks of 3.83 (95% CI 0.97-15.1), 4.40 (1.16-16.7), 4.78 (1.27-18.0), 6.69 (1.71-26.1), and 15.8 (3.72-67.1) were associated with histamine thresholds of 32 g/L, 16 g/L, 8 g/L, 4 g/L, and 1 g/L, respectively, compared with no hyper-responsiveness. These risks were adjusted for sex, age, smoking, lung function, body-mass index, positive skin tests, eosinophilia, asthma, and city of residence. INTERPRETATION: Increased histamine airway hyper-responsiveness predicts mortality from COPD. Although this trend was more pronounced in smokers, an increasing proportion of COPD deaths with increasing hyper-responsiveness was also present among individuals who had never smoked.

Lung function in young adults predicts airflow obstruction 20 years later

         (Kalhan, Arynchyn et al. 2010) Download

OBJECTIVE: The burden of obstructive lung disease is increasing, yet there are limited data on its natural history in young adults. To determine in a prospective cohort of generally healthy young adults the influence of early adult lung function on the presence of airflow obstruction in middle age. METHODS: A longitudinal study was performed of 2496 adults who were 18 to 30 years of age at entry, did not report having asthma, and returned at year 20. Airflow obstruction was defined as an forced expiratory volume in 1 second/forced vital capacity ratio less than the lower limit of normal. RESULTS: Airflow obstruction was present in 6.9% and 7.8% of participants at years 0 and 20, respectively. Less than 10% of participants with airflow obstruction self-reported chronic obstructive pulmonary disease. In cross-sectional analyses, airflow obstruction was associated with less education, smoking, and self-reported chronic obstructive pulmonary disease. Low forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity ratio, and airflow obstruction in young adults were associated with low lung function and airflow obstruction 20 years later. Of those with airflow obstruction at year 0, 52% had airflow obstruction 20 years later. The forced expiratory volume in 1 second/forced vital capacity at year 0 was highly predictive of airflow obstruction 20 years later (c-statistic 0.91; 95% confidence interval, 0.89-0.93). The effect of cigarette smoking on lung function decline with age was most evident in young adults with preexisting airflow obstruction. CONCLUSION: Airflow obstruction is mostly unrecognized in young and middle-aged adults. Low forced expiratory volume in 1 second, low forced expiratory volume in 1 second/forced vital capacity ratio, airflow obstruction in young adults, and smoking are highly predictive of low lung function and airflow obstruction in middle age.


AAT as a diagnostic tool

            (Lisowska-Myjak 2005) Download

Serum alpha-1-antitrypsin (AAT) concentration can be affected by both inflammatory and non-inflammatory conditions. This paper characterizes the nature of AAT in physiology and pathologic deficiency and increasing states. The relationships between the AAT concentration in different clinical materials (serum, urine, faeces) and various diseases connected with different organs were analyzed.

Association of lung function with cognitive decline and dementia: the Atherosclerosis Risk in Communities (ARIC) Study

            (Pathan, Gottesman et al. 2011) Download

BACKGROUND: Previous studies reported a higher risk of cognitive decline and dementia amongst individuals with impaired lung function. However, many did not adjust for important confounders or did not include women and non-whites. METHODS: We studied 10,975 men and women aged 47-70 years (23% African-Americans) enrolled in the Atherosclerosis Risk in Communities Study. Pulmonary function tests and a cognitive assessment, including the Delayed Word Recall, the Digit Symbol Substitution, and the World Fluency Tests, were carried out in 1990-1992. Repeated cognitive assessments were performed in 1996-1998 for the entire cohort, and in 1993-1995, and 2004-2006 in 904 eligible individuals. Dementia hospitalization was ascertained through 2005. RESULTS: In analysis adjusted for lifestyles, APOE genotype, and cardiovascular risk factors, impaired lung function was associated with worse cognitive function at baseline. No association was found between lung function and cognitive decline over time. Impaired lung function at baseline was associated with higher risk of dementia hospitalization during follow-up, particularly amongst younger individuals. The hazard ratios (95% confidence intervals) of dementia hospitalization were 1.6 (0.9, 2.8) and 2.1 (1.2, 3.7) comparing the lowest with the highest quartile of forced expiratory volume in 1 s and forced vital capacity, respectively. Presence of a restrictive ventilatory pattern, but not of an obstructive pattern, was associated with reduced cognitive scores and higher dementia risk. CONCLUSION: Reduced lung function was associated with worse performance in cognitive assessments and with an increased risk of dementia hospitalization. Future research should determine whether maintaining optimal pulmonary health might prevent cognitive impairment and dementia.


Respiratory failure was improved by growth hormone substitution in a patient with hypopituitarism

            (Sato, Yokoyama et al. 2010) Download

A 33-year-old man was referred to the Department of Respiratory Medicine in our hospital due to severe hypercapnic respiratory failure in March 2008. His respiratory function test showed severe restrictive pulmonary dysfunction, and respiratory muscle strength assessed by measuring maximal static expiratory and inspiratory mouth pressures was severely impaired. After non-invasive positive pressure ventilation was started, he was referred to the Endocrinology Department as he was diagnosed as hypopituitarism in his childhood. Pituitary MRI demonstrated pituitary stalk agenesis, and hormonal examination showed that he had severe growth hormone (GH) deficiency. GH replacement therapy was started in August 2008 and his arterial blood gas values and respiratory muscle strength were improved in 6 months. The current case demonstrated that GH deficiency could be a cause of severe respiratory failure.

Effect of aging on respiratory system physiology and immunology

            (Sharma and Goodwin 2006) Download

With the looming expansion of the elderly population of the US, a thorough understanding of "normal" aging-related changes on the respiratory system is paramount. The respiratory system undergoes various anatomical, physiological and immunological changes with age. The structural changes include chest wall and thoracic spine deformities which impairs the total respiratory system compliance leading to increase work of breathing. The lung parenchyma loses its supporting structure causing dilation of air spaces: "senile emphysema". Respiratory muscle strength decreases with age and can impair effective cough, which is important for airway clearance. The lung matures by age 20-25 years, and thereafter aging is associated with progressive decline in lung function. The alveolar dead space increases with age, affecting arterial oxygen without impairing the carbon dioxide elimination. The airways receptors undergo functional changes with age and are less likely to respond to drugs used in younger counterparts to treat the same disorders. Older adults have decreased sensation of dyspnea and diminished ventilatory response to hypoxia and hypercapnia, making them more vulnerable to ventilatory failure during high demand states (ie, heart failure, pneumonia, etc) and possible poor outcomes.


Association of lung function with physical, mental and cognitive function in early old age

            (Singh-Manoux, Dugravot et al. 2011) Download

Lung function predicts mortality; whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in 1 s, height FEV(1)), walking speed (2.44 m), cognitive function (memory and reasoning) and self-reported physical and mental functioning (SF-36) were available on 4,443 individuals, aged 50-74 years. In models adjusted for age, 1 standard deviation (SD) higher height-adjusted FEV(1) was associated with greater walking speed (beta=0.16, 95% CI: 0.13, 0.19), memory (beta=0.09, 95% CI: 0.06, 0.12), reasoning (beta=0.16, 95% CI: 0.13, 0.19) and self-reported physical functioning (beta=0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), body mass index (BMI) and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good 'summary' measure of overall functioning in early old age.

Association between lung function and cognition among children in a prospective birth cohort study

            (Suglia, Wright et al. 2008) Download

OBJECTIVES: To examine the relationship between lung function and cognition among children in the Maternal-Infant Smoking Study of East Boston, a prospective cohort of women and children enrolled before 20 weeks of gestation. A number of studies have demonstrated a relationship between lung function and cognition among adults, but this relationship has not been studied among children. METHODS: At 6 years of age, children completed lung function tests. At 9 years of age, the Wide Range Assessment of Memory and Learning (WRAML) and Kaufman Brief Intelligence Test (K-BIT) were administered. Linear regression was used to assess the relationship between cognition and lung function. RESULTS: The sample of 165 children included 53% girls and 52% Hispanic. Mean (+/- standard deviation) forced expiratory volume in 1 second (FEV (1)) was 1.26 +/- 0.2 L; mean forced vital capacity (FVC) was 1.37 +/- 0.2 L. In multivariate regression, a 1% increase from expected FEV(1) was associated with increases in the matrices and composite subscales of the K-BIT (p < .05), and in the verbal and learning subscales of the WRAML (p < .10). FVC was associated with increases in the composite and matrices subscale of the KBIT and in the visual and learning subscales of the WRAML (all p < .05). CONCLUSION: Increased lung function was associated with increased cognitive development among children after adjusting for tobacco exposure, birthweight, and peak blood lead. Lung and cognitive function may operate under common regulatory processes and thus have shared vulnerabilities to a host of environmental factors during development.

Asthma in the Elderly: Can We Distinguish It from COPD?

            (Tzortzaki, Proklou et al. 2011) Download

Asthma in older adults affects quality of life and results in a higher hospitalization rate and mortality. In common clinical practice, asthma in the elderly is underdiagnosed and undertreated or overdiagnosed and mistreated. The age-related reduction in perception of shortness of breath and the high incidence of comorbidities make the diagnosis and management more difficult and challenging for the physicians. Chronic obstructive pulmonary disease (COPD) is usually easy to distinguish from asthma, but sometimes the distinction from late-onset asthma in older patients, particularly in cigarette smokers, is difficult and may be impossible. Both diseases are characterized by the presence of airflow obstruction but have distinct pathogenesis, inflammatory pattern, and prognosis. The distinction between Asthma and COPD based simply on spirometric parameters is difficult especially in the elderly asthmatics. The combination of lung function testing, bronchial hyperresponsiveness (BHR) and atopy status, HRCT scans, and the newly developed biological techniques, allowing the assessment of biomarker profiles, could facilitate the distinction between these diseases.

Fibrinogen, chronic obstructive pulmonary disease (COPD) and outcomes in two United States cohorts

            (Valvi, Mannino et al. 2012) Download

BACKGROUND: Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). METHODS: We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations. RESULTS: Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period. The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL. Subjects with Stage 3 or 4 COPD were more likely to have a fibrinogen level >393.0 mg/dL (odds ratio 2.28, 95% confidence interval [CI]: 1.79-2.95). In the longitudinal adjusted models, fibrinogen levels >393 mg/dL predicted mortality (hazards ratio 1.54, 95% CI: 1.39-1.70), COPD-related hospitalization (hazards ratio 1.45, 95% CI: 1.27-1.67), and incident Stage 2 COPD (odds ratio 1.36, 95% CI: 1.07-1.74). Similar findings were seen with continuous fibrinogen levels. CONCLUSION: In the Atherosclerosis Risk in Communities/Cardiovascular Health Studies cohort data, higher fibrinogen levels are predictors of mortality, COPD-related hospitalizations, and incident Stage 2 COPD.

Update on the "Dutch hypothesis" for chronic respiratory disease

            (Vestbo and Prescott 1998) Download

BACKGROUND: Many patients with chronic obstructive lung disease show increased airways responsiveness to histamine. We investigated the hypothesis that increased airways responsiveness predicts the development and remission of chronic respiratory symptoms. METHODS: We used data from 24-year follow-up (1965-90) of 2684 participants in a cohort study in Vlagtwedde and Vlaardingen, Netherlands. Increased airways responsiveness was defined as a PC10 value (concentration of histamine for which challenge led to a 10% fall in forced expiratory volume in 1 s) of less than 8 mg/ml. Information on respiratory symptoms was collected by means of a standard questionnaire every 3 years. Logistic regression was used to control for age, area of residence, cigarette smoking status, and sex. FINDINGS: Participants with increased airways responsiveness (1281 observations) were more likely than those without increased airways responsiveness (5801 observations) to develop the following symptoms during any 3-year follow-up interval: chronic cough (odds ratio 1.9 [95% CI 1.2-2.9]), chronic phlegm (2.0 [1.3-3.0]), dyspnoea (2.3[1.5-3.5]), asthmatic attacks (3.7[2.2-6.1]), and persistent wheeze (2.7[1.7-4.4]). The estimate of the odds ratio for the development of any of the six symptoms was 1.7 (1.2-2.3). Participants with increased airways responsiveness were less likely than those without this characteristic to show remission of these respiratory symptoms. The estimate of the odds ratio for the remission of any of the six symptoms was 0.42 (0.28-0.61). INTERPRETATION: These prospective analyses show that increased airways responsiveness is positively associated with the development of chronic respiratory symptoms and negatively associated with the remission of these symptoms in adults.


Forced expiratory volume in 1 second and cognitive aging in men

         (Weuve, Glymour et al. 2011) Download

OBJECTIVES: To evaluate forced expiratory volume in 1 second (FEV(1) , a measure of overall lung function), long-term average FEV(1) , and rate of decline in FEV(1) in relation to cognition and cognitive decline in older men. DESIGN: Prospective observational study. SETTING: Community-based population. PARTICIPANTS: Eight hundred sixty-four older men from the Normative Aging Study. MEASUREMENTS: Starting in 1984, participants underwent triennial clinical evaluations. Lung function assessments provided estimates of FEV(1) . Cognitive assessments entailing tests of several cognitive abilities began in 1993. FEV(1) measured approximately 12 years before baseline cognitive testing, average FEV(1) over the 12-year period, and rate of change in FEV(1) were all evaluated in relation to baseline and change in performance on the cognitive tests. RESULTS: In multivariable-adjusted analyses, associations between FEV(1) and baseline cognitive scores were mixed, although average FEV(1) predicted significantly better performance on tests of visuospatial ability (P=.04) and general cognition (P=.03). Higher FEV(1) was more consistently associated with slower cognitive decline, but only the association between historical FEV(1) and attention was significant (difference per standard deviation in FEV(1) =0.056, P=.05). Rate of FEV(1) decline was not consistently associated with cognitive function or decline. Findings were generally similar or stronger in men who had never smoked. To account for potential bias due to selective attrition, inverse probability of censoring weights were applied to the cognitive decline analyses, yielding slightly larger estimates; the inadequate prognostic power of the censoring models limited this approach. CONCLUSION: Overall, the data provide limited evidence of an inverse association between FEV(1) and cognitive aging.


References

Chyou, P. H., L. R. White, et al. (1996). "Pulmonary function measures as predictors and correlates of cognitive functioning in later life." Am J Epidemiol 143(8): 750-6 PMID: 8610684

Duvoix, A., J. Dickens, et al. (2012). "Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease." Thorax PMID: 22744884

Dyer, C. (2012). "The interaction of ageing and lung disease." Chron Respir Dis 9(1): 63-7 PMID: 22308556

Giltay, E. J., A. Nissinen, et al. (2009). "Apolipoprotein E genotype modifies the association between midlife lung function and cognitive function in old age." Dement Geriatr Cogn Disord 28(5): 433-41 PMID: 19907180

Hospers, J. J., D. S. Postma, et al. (2000). "Histamine airway hyper-responsiveness and mortality from chronic obstructive pulmonary disease: a cohort study." Lancet 356(9238): 1313-7 PMID: 11073020

Kalhan, R., A. Arynchyn, et al. (2010). "Lung function in young adults predicts airflow obstruction 20 years later." Am J Med 123(5): 468 e1-7 PMID: 20399325

Lisowska-Myjak, B. (2005). "AAT as a diagnostic tool." Clin Chim Acta 352(1-2): 1-13 PMID: 15653097

Pathan, S. S., R. F. Gottesman, et al. (2011). "Association of lung function with cognitive decline and dementia: the Atherosclerosis Risk in Communities (ARIC) Study." Eur J Neurol 18(6): 888-98 PMID: 21244584

Sato, I., Y. Yokoyama, et al. (2010). "Respiratory failure was improved by growth hormone substitution in a patient with hypopituitarism." BMJ Case Rep 2010 PMID: 22766570

Sharma, G. and J. Goodwin (2006). "Effect of aging on respiratory system physiology and immunology." Clin Interv Aging 1(3): 253-60 PMID: 18046878

Singh-Manoux, A., A. Dugravot, et al. (2011). "Association of lung function with physical, mental and cognitive function in early old age." Age (Dordr) 33(3): 385-92 PMID: 20878489

Suglia, S. F., R. O. Wright, et al. (2008). "Association between lung function and cognition among children in a prospective birth cohort study." Psychosom Med 70(3): 356-62 PMID: 18378869

Tzortzaki, E. G., A. Proklou, et al. (2011). "Asthma in the Elderly: Can We Distinguish It from COPD?" J Allergy (Cairo) 2011: 843543 PMID: 21785614

Valvi, D., D. M. Mannino, et al. (2012). "Fibrinogen, chronic obstructive pulmonary disease (COPD) and outcomes in two United States cohorts." Int J Chron Obstruct Pulmon Dis 7: 173-82 PMID: 22419864

Vestbo, J. and E. Prescott (1998). "Update on the "Dutch hypothesis" for chronic respiratory disease." Thorax 53 Suppl 2: S15-9 PMID: 10193342

Weuve, J., M. M. Glymour, et al. (2011). "Forced expiratory volume in 1 second and cognitive aging in men." J Am Geriatr Soc 59(7): 1283-92 PMID: 21718272