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Lung function - clinical importance, problems, and new results

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This review tackles the usefulness of spirometry, a more than century old method of assessing pulmonary lung function. Variables measured with a spirometer, such as forced expiratory volume in 1 s, have long been the mainstays of the diagnosis and treatment of lung disorders. But there are problems with the reliability of spirometric measurements. The method depends on the cooperation of the investigated subject, which introduces a confounding subjective element and all too often results in test failure, and the results are evaluated against the predicted values that are based on a set of fixed factors, some of which, such as body height, are not in a straight proportion to the intrathoracic gas volume. Substantial spread of results arises, which makes a reliable assessment of lung function difficult. New methods, such as the resistance-volume curve, provide better information on airway behavior in different conditions. These new methods, which basically evolved from spirometry, show that the old idea of lung function analysis is still viable and may remain helpful for diagnosis and treatment of respiratory pathological states.
Toxocariasis has been highlighted as a potentially important neglected infection of poverty in developed countries that experience substantive health disparities such as the United States. An association between Toxocara infection and lung function, in concert with a relatively high prevalence of infection, may mark an important mechanism by which this infection could contribute significantly to the differential morbidity across different socioeconomic groups and landscapes. To assess the potential relevance of this infection in a dense urban environment, we measured the association between forced expiratory volume in 1 second (FEV1) and serology diagnosed Toxocara infection in a sample of US-born New York City residents. We identified a significant independent association between Toxocara infection and lung function, wherein those with previous Toxocara infection had a 236.9 mL reduced FEV1 compared to those without Toxocara infection even after adjusting for age, sex, ethnicity, level of education, smoking status, body mass index, and pet ownership. These findings from New York City corroborate similar findings in a national sample and, while the cross-sectional data preclude a direct causal relationship, this study identifies a potentially important neglected infection in a dense urban landscape.
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New insights into physiology and pathophysiology by resistance-volume recordings

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This work deals with the assessment of airway resistance in the course of a single breath. The study showed the presence of an early increase in the resistance at the beginning of expiration, which intensifies during expiration and ends up with a sharp decline during expiring the last remaining volume of ca 350 ml. The dynamic changes in airway resistance over a breath depend on the disharmonic interplay between diaphragm function and bronchial wall tonus. Thus, airway resistance is not constant during breathing, as could be misleadingly judged from the total resistance averaged over a breath. The study underscores the importance of recording the resistance-volume curves alongside the standard flow-volume curves to be able to discern the peculiarities of airway resistance changes during a single breath. Knowing changes in the instantaneous airway resistance characteristic for a given lung pathology could appreciably improve the diagnostic and therapeutic powers.
Inhaled corticosteroids (ICS) are widely used for the treatment of COPD despite of controversial statements concerning their efficacy. The use of N-acetylcysteine (NAC), a mucolytic drug with antioxidant properties, is less clear, but it may counteract the oxidant-antioxidant imbalance in COPD. The aim of this study was to evaluate whether treatment of COPD patients with ICS or NAC is able to improve inflammatory indices and to enhance lung function. ICS treatment enhanced protective markers for oxidative stress such as glutathione peroxidase (GPx) (51.2 ±5.8 vs. 62.2 ±8.6 U/g Hb, P<0.02) and trolox-equivalent antioxidant capacity (TEAC) (1.44 ±0.05 vs. 1.52 ±0.06 mM, P<0.05). NAC decreased sputum eosinophil cationic protein (318 ±73 vs. 163 ±30 ng/ml, P<0.01) and sputum IL-8 (429 ±80 vs. 347 ±70 ng/ml, P<0.05). The increased antioxidant capacity prevented an up-regulation of adhesion molecules, since the levels of intracellular adhesion molecule 1 (ICAM-1) correlated negatively with GPx (P<0.0001) and TEAC (P<0.0001). On the other hand, expression of adhesion molecules was promoted by inflammation, reflected by a positive correlation between the levels of IL-8 and ICAM-1 (P<0.0001). The effects of treatment on lung function were only reflected in the FEV1 values. The absolute value of FEV1, both before and after salbutamol inhalation, increased from 1690 ±98 to 1764 ±110 ml, and 1818 ±106 to 1906 ±116 ml, respectively, after ICS (P<0.05) . Ten weeks after treatment, FEV1 values dropped to 1716 ±120 ml post-salbutamol (P<0.05). When followed by treatment with NAC, these values decreased even further to 1666 ±84 ml. These results suggest that ICS improved lung function in COPD patients with moderate airflow obstruction, beside a minor improvement in the oxidant-antioxidant imbalance leading to a lesser expression of ICAM-1. Treatment with NAC decreased some inflammatory parameters and had indirectly an inhibitory effect on the expression of adhesion molecules.
Sarcoidosis is a chronic inflammatory multiorgan disease of unknown origin. Our previous study demonstrated a significant correlation between the relative count of nonCD4+, nonCD8+ lymphocytes in bronchoalveolar lavage of active sarcoidosis patients and proangiogenic activity of BAL homogenates. The aim of the present study was to evaluate in a group of 40 patients with active sarcoidosis the possible relationship between the intensity of alveolitis, particularly the nonCD4+, nonCD8+ lymphocyte subset, and other parameters characterizing the level of pulmonary (lung function tests) and extrapulmonary (spleen longitudinal dimension) disease activity. We found that the relative count of nonCD4+, nonCD8+ lymphocytes in BAL correlated positively with spleen size (r=0.50, P<0.01) and negatively with static compliance (r=0.43, P<0.05). We concluded that the lymphocytes belonging to the nonCD4+nonCD8+ subset participate in the inflammatory process in sarcoidosis. However, more detailed phenotypic and functional characteristics of this cellular population are needed.
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Pulmonary function between 40 and 80 years of age

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Spirometry is the most frequently performed lung function test. To determine a normal range of spirometry results, reference formulas are used. Predicted values play an important role in establishing whether the volumes measured in an individual fall within a range to be expected in a healthy person of the same gender, height, and age. Such standards enable to assess the development of the respiratory system in the youth, the early recognition of the influence of a disease on the respiratory system and the influence of environmental factors on lung function. The objective of the present study was to estimate lung function prediction equations and to identify appropriate normal reference values for the Lublin Region local population of adults. We addressed the issue by analyzing the data from a lung function screening program conducted in the Lublin Region of Poland. Pulmonary function of adults aged 40-80 years was assessed from the measurements of forced vital capacity (FVC) and forced expired volume in the first second (FEV1) in 136 adults. Reference values of FVC and FEV1 for females and males were calculated by linear multiple regressions with age and height used as predictors. Different equations were compared to show their reliability when applied to the local population. The results were as follows. In females, the mean FEV1 was 2.856 ±0.534 (L) (113.7 ±14.3%) and the mean FVC was 3.517 ±0.662 (L) (118.5 ±14.1%), in males, 3.913 ±0.773 (L) (110.9 ±15.1%), 4.922 ±0.941 (L) (112.1 ±14.1%), respectively. The estimated prediction equations were: for the FVC - for females - FVC (L) = 0.0528 (height) - 0.0262 (age) - 3.676 and for males - FVC = 0.0756 (height) - 0.0649 (age) - 4.904; and for the FEV1 - for females - FEV1 (L) = 0.0378 (height) - 0.0282 (age) - 1.799 and for males - FEV1 (L) = 0.0553 (height) - 0.0553 (age) - 2.874. Units are years for age and centimeters for height. In conclusion, the analysis of the lung function data showed that there were significant difficulties in determining the appropriate reference values of FEV1 and FVC. The predicted FEV1 and FVC values derived from equations based on the ECSC (1) reference populations are considerably lower than those calculated in the present study, re-emphasizing the need to be cautious when applying the ECSC reference values for the local Lublin population. There seems to be a need for a constant refinement of spirometric standards.
Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction. Clinical symptoms are caused by weakness and increased fatigability of various muscle groups. Myasthenia may lead to significant respiratory dysfunction. The aim of our study was to estimate lung function in children with MG. We tested 23 non-smoking patients (18 girls and 5 boys) aged 7-18 years. Whole-body plethysmography and spirometry were performed in all patients. In 33% of the patients a decrease in VC <80% of predicted value was observed (VC = 89 ±19%), but the analysis of TLC revealed restrictive pattern only in one patient (TLC = 102 ±17%). In more than 75% of the children the value of RV above 120% of predicted value was found (RV = 146 ±54%). Spirometric obstructive pattern measured by FEV1%VC <70% was not observed, although in 56% of the patients airway resistance was increased (Raw = 132 ±44%). In 45% of the patients a decrease of PEF (76 ±14%) was observed. In MG children true restrictive pulmonary impairment is rarely observed and a decrease in VC in these patents seems to result mainly from functional restriction provoked by an increase in RV. Spirometry is not an optimum method to assess functional changes in MG patients. The assessment of additional measures such as TLC, RV, and Raw is desirable.
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The natural history of respiratory system function

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Lung growth starts in the first year of life. Between 20-30 years of age, man achieves the maximum FEV1. Some years later, maximum FVC is achieved. After the phase of a dynamic increase, lung function stabilizes for a while. Thereafter, it starts declining slowly in some individuals or increasing in others. The third and last phase of lung function changes during a lifetime begins between 40-45 years of life. The FEV1 and some years later also FVC diminish with a varied speed during this period. Changes in FVE1 and FVC in the third phase are slower at the beginning and accelerate in the six or seventh decade of life. There are some differences between males and females concerning the lung function profile. Female lung function starts decreasing earlier than that in male individuals. There are also pronounced interindividual differences in lung function among individuals of a similar age and body height.
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Ventilatory response to hypoxia in experimental pathology of the diaphragm

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In this study, we examined the usefulness of arterial blood gas variables, as changed by the hypoxic stimulus, in discerning various experimentally-induced conditions of diaphragm weakness in anesthetized cats. We defined three experimental situations (models): (i) intact muscle, statistical Class I, (ii) four degrees of muscle dysfunction (after sequential diaphragm denervation), Classes II-V, and (iii) entirely paralyzed muscle, Class VI. Responses to a hypoxic stimulus in the above-mentioned conditions were evaluated by using the methods of the pattern recognition theory. We found that before the hypoxic stimulus, with partial but of different severity denervation of the diaphragm, the k-nearest neighbor classifier (k-NN) assigned 100% of the classified cases to Class II (one phrenic nerve rootlet cut). In contrast, during hypoxia only 67% of cases were assigned to Class II, the remaining being spread throughout other classes of muscle weakness. When one limits the procedure to the extreme classes: Class I (intact diaphragm) and Class VI (totally denervated diaphragm), the k-NN picks out 33% and 50% cases of bilateral diaphragm paralysis before and during hypoxia, respectively. We conclude that any remaining innervations of the diaphragm ensure the functionally optimal level of lung ventilation that may waver when hypoxia develops.
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