Diffusion Reaction of Carbon Monoxide in the Human Lung.

The capture of CO, a standard lung function test, results from diffusion-reaction processes of CO with hemoglobin inside red blood cells (RBCs). In its current understanding, suggested by Roughton and Forster in 1957, the capture is represented by two independent resistances in series, one for diffusion from the gas to the RBC periphery, the second for internal diffusion reaction. Numerical studies in 3D model structures described here contradict the independence hypothesis. This results from two different theoretical reasons: (i) The RBC peripheries are not equi-concentrations; (ii) diffusion times in series are not additive.

The Roughton-Forster equation for DLCO and DLNO re-examined.

Roughton and Forster (RF) proposed to split the lung diffusing capacity into two contributions describing first, diffusion to red blood cells (RBC), and second, capture by diffusion from the RBC surface and reaction with haemoglobin. Solving the diffusion-reaction equations for simplified capillary-RBC structures, we investigate the RF interpretation. This reveals first that the conventional extrapolation to zero pressure of 1/DLCO on PO2 is not a correct measure of the diffusive component. Consequently the capillary volumes deduced from this extrapolation are erroneous. Secondly, capture mechanisms are different for CO and NO: while DLCO characterizes "volume absorption" in the RBC and is correlated with hematocrit, DLNO quantifies "surface absorption" and provide information about the morphology of the space between the alveolar surface and the RBC surfaces. In conclusion, the RF approach may lead to erroneous physiological interpretations of DLCO; nevertheless, the measurement of DLCO and DLNO bring different types of information that give the potential for a better understanding of respiratory diseases.

Partial versus maximal forced exhalations in COPD: enhanced signal detection for novel therapies.

BACKGROUND: Evaluation of novel compounds for COPD often relies on FEV1 for signal detection. Partial forced exhalations from end-tidal inspiration (PEFV) might complement FEV1 in identifying such a signal. We examined the prevalence of bronchodilator response (BDR) using PEFV and FEV1 in patients with COPD. METHODS: 110 consecutive COPD patients were tested prospectively with PEFV and maximal expiratory flow before and after inhalation of a short-acting ß2 agonist (salbutamol, 400 µg). Partial flow at 800 ml above residual volume was derived from the PEFV (PF800). Significant changes in PF800 and/or FEV1 were set at the upper 95% confidence interval after placebo (n = 28). RESULTS: Four groups were identified by the presence (+) or absence (-) of a BDR: Group 1 [PF800 (-)FEV1(-)] when no change was observed (n = 31), Group 2 [PF800(+)FEV1(-)] when PF800 alone improved (n = 31), Group 3 [PF800(-)FEV1(+)] when FEV1 alone improved (n = 26), and Group 4 [PF800(+)FEV1(+)] when both variables improved (n = 18). There were 35 non-responders in any parameter, and 75/110 subjects who showed a response in at least one parameter. The changes in PF800 and FEV1 were not correlated suggesting these assess different airway generations. CONCLUSIONS: The use of PF800 increased detection of a BDR in COPD compared to FEV1 alone and may reflect small airway responses. The PEFV maneuver is simple, repeatable and may avoid some of the theoretical disadvantages of FEV1. The role of PF800 for evaluating novel anti-inflammatory agents remains to be determined.

Is there a competition for oxygen availability between respiratory and limb muscles?

If a competition between the oxygen demands of limb and respiratory muscles happens, hypoxia may favor redistribution of blood flow from peripheral to respiratory muscles during heavy exercise. This hypothesis was tested in eighteen lowlanders and 27 highlanders at 4350m altitude. During an incremental exercise, the regional tissue oxygen saturation (rSO2) and tissue hemoglobin concentration ([Hbt]) of the intercostal muscles and vastus medialis were monitored simultaneously by NIRS. The intercostal and vastus medialis rSO2 values were lower at altitude than at sea level (-10%, p<0.001) and decreased similarly during incremental exercise (p<0.001) while [Hbt] values increased. At maximal exercise, the intercostal rSO2 was lower than the vastus medialis rSO2 in lowlanders (-7%, p<0.001). In highlanders the time patterns were similar but intercostal rSO2 was less decreased at exercise (p<0.05). Maximal exercise performed in hypoxia did not alter the kinetics of rSO2 and [Hbt] in peripheral muscles. These findings do not favor the hypothesis of blood flow redistribution.

Swallowing disorders, pneumonia and respiratory tract infectious disease in the elderly.

Swallowing disorders (or dysphagia) are common in the elderly and their prevalence is often underestimated. They may result in serious complications including dehydration, malnutrition, airway obstruction, aspiration pneumonia (infectious process) or pneumonitis (chemical injury caused by the inhalation of sterile gastric contents). Moreover the repercussions of dysphagia are not only physical but also emotional and social, leading to depression, altered quality of life, and social isolation. While some changes in swallowing may be a natural result of aging, dysphagia in the elderly is mainly due to central nervous system diseases such as stroke, parkinsonism, dementia, medications, local oral and oesophageal factors. To be effective, management requires a multidisciplinary team approach and a careful assessment of the patient's oropharyngeal anatomy and physiology, medical and nutritional status, cognition, language and behaviour. Clinical evaluation can be completed by a videofluoroscopic study which enables observation of bolus movement and movements of the oral cavity, pharynx and larynx throughout the swallow. The treatment depends on the underlying cause, extent of dysphagia and prognosis. Various categories of treatment are available, including compensatory strategies (postural changes and dietary modification), direct or indirect therapy techniques (swallow manoeuvres, medication and surgical procedures).

[Swallowing disorders, pneumonia and respiratory tract infectious disease in the elderly]. / Troubles de la déglutition du sujet âgé et pneumopathies en 14 questions/réponses.

Swallowing disorders (or dysphagia) are common in the elderly and their prevalence is often underestimated. They may result in serious complications including dehydration, malnutrition, airway obstruction, aspiration pneumonia (infectious process) or pneumonitis (chemical injury caused by the inhalation of sterile gastric contents). Moreover the repercussions of dysphagia are not only physical but also emotional and social, leading to depression, altered quality of life, and social isolation. While some changes in swallowing may be a natural result of aging, dysphagia in the elderly is mainly due to central nervous system diseases such as stroke, parkinsonism, dementia, medications, local oral and oesophageal factors. To be effective, management requires a multidisciplinary team approach and a careful assessment of the patient's oropharyngeal anatomy and physiology, medical and nutritional status, cognition, language and behaviour. Clinical evaluation can be completed by a videofluoroscopic study which enables observation of bolus movement and movements of the oral cavity, pharynx and larynx throughout the swallow. The treatment depends on the underlying cause, extent of dysphagia and prognosis. Various categories of treatment are available, including compensatory strategies (postural changes and dietary modification), direct or indirect therapy techniques (swallow manoeuvres, medication and surgical procedures).

[Practical methods for controlled diaphragmatic breathing in 2009: proposals for a consensus]. / Modalités pratiques de réalisation de la ventilation dirigée abdomino-diaphragmatique en 2009: propositions pour un consensus.

BACKGROUND: This work has been completed at the request of the French Language Society of Pneumology. It is the result of collaboration between the 'Muscles and Respiration Group' and the 'Working Group in Physiotherapy', arriving at a consensus on diaphragmatic breathing. RESULTS: From the literature followed by a formalized consensus methodology, the authors specify the terminology and define the appropriate methods of this technique that should be used. CONCLUSION: Analysis of the literature to date does not allow assessment of the efficacy of this technique. The precise definition of the methods of diaphragmatic breathing as proposed in the present study will be used as a basis for forthcoming studies on this technique.

[Evaluation and follow up of hyperinflation in COPD]. / Comment mesurer et suivre la distension pulmonaire au cours de la BPCO.

Plethysmography is the reference method and requires rigorous methodology, particularly in patients with severe airflow limitation. Dilution techniques (nitrogen or most often helium) may underestimate true lung volumes as they do not measure trapped gas. Inspiratory capacity is the only available method to evaluate exercise induced dynamic hyperinflation. It is an imperfect surrogate of plethysmography for evaluating the reversibility of hyperinflation with bronchodilators. Resting hyperventilation has recently been shown to be a sensitive method to detect dynamic hyperinflation. Evaluation of hyperinflation is an important criterion in the phenotyping of COPD patients. However, its natural history remains at present poorly defined.

[Atopic dermatitis aggravates the allergic airways inflammation in acute viral bronchiolitis]. / La dermatite atopique aggrave l'inflammation allergique dans la bronchiolite aiguë virale.

INTRODUCTION: Exhaled nitric oxide (FeNO) is a putative non-invasive marker of eosinophilic airway inflammation with a good predictive value for allergic asthma in preschool children. The aim of the present study was to compare FeNO after acute viral bronchiolitis (AVB) in children aged less than 2 years without atopic dermatitis (AD) vs those with atopic dermatitis, as well as children with AD without any history of AVB. METHODS: Forty-two children (mean age +/- SD: 12.3 +/- 5.2 months; range 5.0-23.5; sex-ratio M: F=1.3: 1) were included in this prospective study, > 8 wks after an episode of AVB. The patients' atopic status was assessed both by clinical phenotype and IgE- mediated response to inhaled and/or food allergens. FeNO (ppb) was measured off-line by the chemoluminescence method on samples obtained from gas collected in a balloon during tidal breathing. RESULTS: There was a significant difference between the AVB/AD (23.4 +/- 14.3 ppb, n=15) vs the AVB without AD group (13.5 +/- 10. 1 ppb, n=13) or the AD without AVB group (11.0 +/- 8.3 ppb, n=14). Maternal feeding for more than 2 months decreased FeNO by 50%. CONCLUSION: Atopic children below 2 years with AD produce more NO after AVB than non-atopic children or atopic children without any history of AVB. Maternal feeding decreases FeNO.

European reference equations for CO and NO lung transfer.

The aim of the present study was to calculate reference equations for carbon monoxide and nitric oxide transfer, measured in two distinct populations. The transfer factor of the lung for nitric oxide (T(L,NO)) and carbon monoxide (T(L,CO)) were measured in 303 people aged 18-94 yrs. Measurements were similarly made in two distant cities, using the single-breath technique. Capillary lung volume (V(c)) and membrane conductance, the diffusing capacity of the membrane (D(m)), for carbon monoxide (D(m,CO)) were derived. The transfer of both gases appeared to depend upon age, height, sex and localisation. The rate of decrease in both transfers increased after the age of 59 yrs. T(L,NO)/alveolar volume (V(A)) and T(L,CO)/V(A) were only age-dependent. The mean T(L,NO)/T(L,CO) was 4.75 and the mean D(m)/V(c) was 6.17 min(-1) x kPa(-1); these parameters were independent of any covariate. V(c) and D(m,CO) calculations depend upon the choice of coefficients included in the Roughton-Forster equation. Values of 1.97 for D(m,NO)/D(m,CO) ratio and 12.86 min x kPa(-1) for 1/red cell CO conductance are recommended. The scatter of transfer reference values in the literature, including the current study, is wide. The present results suggest that differences might be due to the populations themselves and not the methods alone.

[Lung cancer in the elderly subject]. / Cancer bronchique du sujet âgé.

INTRODUCTION: In France, the average age for the diagnosis of bronchial carcinoma is 64. It is 76 in the population of over 70. In fact, its incidence increases with age linked intrinsic risk of developing a cancer and with general ageing of the population. Diagnosis tools are the same for elderlies than for younger patients, and positive diagnosis mainly depends on fibreoptic bronchoscopy, complications of which being comparable to those observed in younger patients. STATE OF THE ART: The assessment of dissemination has been modified in recent years by the availability of PET scanning which is increasingly becoming the examination of choice for preventing unnecessary surgical intervention, a fortiori in elderly subjects. Cerebral imaging by tomodensitometry and nuclear magnetic resonance should systematically be obtained before proposing chirurgical treatment. An assessment of the general state of health of the elderly subject is an essential step before the therapeutic decision is made. This depends on the concept of geriatric evaluation: Geriatric Multidimensional Assessment, and the Comprehensive Geriatric Assessment which concerns overall competence of the elderly. PERSPECTIVES: This is a global approach that allows precise definition and ranking of the patient's problems and their impact on daily life and social environment. Certain geriatric variables (IADL, BADL, MMSE, IMC etc) may be predictive of survival rates after chemotherapy or the incidence of complications following thoracic surgery. The main therapeutic principles for the management of bronchial carcinoma are applicable to the elderly subject; long term survival without relapse after surgical resection is independent of age. Whether the oncological strategy is curative or palliative, the elderly patient with bronchial carcinoma should receive supportive treatments. They should be integrated into a palliative programme if such is the case. In fact, age alone is not a factor that should detract from optimal oncological management. CONCLUSIONS: The development of an individual management programme for an elderly patient suffering from bronchial carcinoma should be based on the combination of oncological investigation and comprehensive geriatric assessment.

Spirometric values in Tunisian children: relationship with pubertal status.

BACKGROUND: Little is known about the effect of pubertal stages on lung function parameters in Tunisian children. AIM: The purpose of this study is to determine the relationship between lung function and pubertal stage in Tunisian children using anthropometric parameters. SUBJECTS AND METHODS: Pulmonary function parameters were measured with a Minato portable spirometer in 684 healthy Tunisian children (351 males and 333 females) aged between 8 and 16. The pubertal status was assessed for males and females according to the Tanner Method. RESULTS: A large variation was observed in the distribution of children's age and height by pubertal stages in both sexes. Height increased with age and pubertal stage in both males and females. The results also showed a significant increase in parameters of lung function (FVC, FEV(1), PEF, MEF(50) and MMEF(25-75)) with pubertal stage in Tunisian children. The analysis of covariance adjusting for anthropometric parameters showed that pubertal status had a significant independent effect on some pulmonary function parameters in both sexes. CONCLUSION: The results indicated that the parameters of pulmonary function for healthy Tunisian school children increased with age, height and pubertal stage. The present study has indicated that the use of only one morphological parameter such as height is not sufficient, but the pubertal status could be taken into account to standardize the lung function.

[Factors influencing pulmonary function in Tunisian women aged 45 years and more]. / Facteurs influençant les variables ventilatoires des Tunisiennes âgées de 45 ans et plus.

INTRODUCTION: The aim of this study was to analyse the factors influencing pulmonary function and inspiratory muscle strength in healthy Tunisian women aged >or=45 years and in particular to determine the effect of parity. METHODS: A medical questionnaire together with an evaluation of sporting activity score and 2 levels for schooling and socio-economic status was administered. Parity was introduced as numeric, as dichotomous (G1:or=4) and in 3 classes (C1:<2; C2:=3-4; C3: > 4). Plethysmography with measurement of airway conductance and maximal inspiratory pressure was performed. RESULTS: 108 women were included. According to the ascending multiple linear regression, and in decreasing order, the following influencing factors are noted: Age and height, parity, weight and daily activity, schooling level, and finally leisure activity, body mass index, and physical activity. With high parity, and especially in women aged >or=60 years, there was a decrease in inspiratory muscle strength and an obstructive tendency, without associated restrictive component. Parity effects are age independent. CONCLUSIONS: Factors influencing the pulmonary function of healthy Tunisian women aged >or=45 years are multiple. Lung function declines with increasing parity.

[Physiological factors influencing pulmonary capillary volume and membrane diffusion]. / Facteurs physiologiques influençant le volume capillaire pulmonaire et la diffusion membranaire.

BACKGROUND: The lung is subject to many physiological changes during life. The aim of this study was to identify factors that influence gas transfer, which depends on membrane diffusion (Dm) and pulmonary capillary blood volume (Vc). METHODS: Dm and Vc measurements were performed at rest in 135 healthy patients divided into three groups according to age and after an exercise in 22 non-trained children. Measurements were made using a simultaneous transfer of 2 gases; nitric oxide (NO) and carbon monoxide (CO). RESULTS: Dm was correlated with height in the adult group and with weight in the elderly group. Vc was not correlated with weight in the three studied groups, but correlated with height in the adult group. Dm and Vc declined with age (p<0.05), For Dm this started at the age of forty whereas a fall in Vc was apparent at sixty. Pulmonary and vascular ageing could explain these results. Sex had no effect on Dm and Vc. Exercise led to a significant rise in Dm and Vc (p<0.05) which was attributed to pulmonary capillary distension and recruitment. CONCLUSION: Knowledge of these physiological changes permits a better understanding of pathological changes.

[Evaluation of pulmonary function in the elderly. Intergroupe Pneumo Gériatrie SPLF-SFGG]. / Evaluation de la fonction respiratoire chez le sujet âgé. Intergroupe Pneumo Gériatrie SPLF-SFGG.

Aging is associated with a progressive decrease in lung function. As a consequence of aging, individual's reserve is diminished, but this decrease is heterogeneous between individual subjects. Many factors are involved in the overall decline in lung function. The prevalence of asthma in the elderly is estimated between 6 and 10%. Mortality due to COPD is increasing, especially among older subjects. Older subjects are at an increased risk of developing chronic diseases such as Parkinson's disease, which can have consequences for lung function. Under-nutrition is also common in the elderly and can produce sarcopenia and skeletal muscle dysfunction. The presentation of respiratory disorders may differ in the elderly, especially because of a lack of perception of symptoms such as dyspnea. The impact of bronchodilatators or corticosteroids on respiratory function has not been studied in the elderly. Drugs usually used for the treatment of hypertension or arrhythmias, which are often observed with aging, can have pulmonary toxicity. There is no difference between functional evaluation in younger and older subjects but it is more difficult to find predicted values for older patients. Performing pulmonary function tests in older patients is often difficult because of a higher prevalence of cognitive impairment and/or poor coordination. When assessing pulmonary function in the elderly, the choice of tests will be depend on the circumstances, with the use of voluntary manoeuvres dependent on the condition of the patient.

[Aging of the lung parenchyma]. / Vieillissement du poumon profond.

INTRODUCTION: The study of lung parenchymal function is focused on the measurement of carbon monoxide diffusing transfer (TLCO) which is a function of both membrane characteristics (Dm) and capillary lung volume (Vc) The objective of this study was to estimate the effect of age on both variables. METHODS: At rest, 134 healthy non-smokers (18-85 year old) were investigated by a double transfer NO-CO method. Capillary pulmonary compliance was estimated by applying a continuous negative pressure (CNP: -10 mmHg) at the mouth to 24 subjects. RESULTS: Significant decreases in VA, TLCO, TLNO, Dm and Vc in relation to age were observed (p < 0.05). CNP induced a significant increase in all variables, the increase in Vc in elderly was greater than that in younger subjects. CONCLUSION: Alveolo capillary membrane aging induces a decrease in Dm and Vc, however the increase in the estimated capillary compliance with CNP could provide an adaptation to the decrease in Vc.