Decrease In Total Lung Capacity Research Articles

High Baseline Serum Clara Cell 16 kDa Predicts Subsequent Lung Disease Worsening in Systemic Sclerosis.

Clara cell secretory protein (CC16) is a sensitive marker of bronchial epithelial cell damage. The CC16 serum level is elevated in patients with pulmonary fibrosis, but its predictive value on lung disease progression has not yet been studied. We aimed to assess the value of serum CC16 concentration in predicting lung disease deterioration in patients with systemic sclerosis (SSc). We prospectively analyzed and followed 106 patients with SSc during a 4-year period for the risk of developing combined deleterious event, defined as a 10% decrease in total lung capacity or forced vital capacity from baseline, or death, according to serum CC16 at inclusion. Receiver-operating characteristic (ROC) curve analysis was performed for prediction of events during the first 2 years after inclusion. Cumulative risks of combined events were computed by Kaplan-Meier analysis. The best cutoff level of serum CC16 for prediction of a combined event was 33 ng/ml, with 76% sensitivity and 65% specificity (area under the ROC curve: 0.71, 95% CI 0.61-0.81, p < 0.0001). Progression of lung disease evaluated by a mean time-to-event differed between patients with high baseline serum CC16 (42.8 mos, 36.3-49.3) and those with low serum CC16 (56.3 mos, 50.9-61.7; log-rank test, p < 0.001). After adjustment for age, duration of disease, clinical and lung function measures, the risk of combined event occurrence in patients with high serum CC16 was significantly higher than in those with low CC16 (HR 2.9, 1.2-6.75, p < 0.05). High baseline serum CC16 predicts lung disease worsening in patients with SSc.

Interprétation et utilisation des explorations fonctionnelles respiratoires de routine de l’adulte : spirométrie, volumes non mobilisables, diffusion, hématose, test de provocation bronchique à la métacholine et test de marche

Resting pulmonary function tests (PFT) include the assessment of ventilatory capacity: spirometry (forced expiratory flows and mobilisable volumes) and static volume assessment, notably using body plethysmography. Spirometry allows the potential definition of obstructive defect, while static volume assessment allows the potential definition of restrictive defect (decrease in total lung capacity) and thoracic hyperinflation (increase in static volumes). It must be kept in mind that this evaluation is incomplete and that an assessment of ventilatory demand is often warranted, especially when facing dyspnoea: evaluation of arterial blood gas (searching for respiratory insufficiency) and measurement of the transfer coefficient of the lung, allowing with the measurement of alveolar volume to calculate the diffusing capacity of the lung for CO (DLCO: assessment of alveolar-capillary wall and capillary blood volume). All these pulmonary function tests have been the subject of an Americano-European Task force (standardisation of lung function testing) published in 2005, and translated in French in 2007. Interpretative strategies for lung function tests have been recommended, which define abnormal lung function tests using the 5th and 95th percentiles of predicted values (lower and upper limits of normal values). Thus, these recommendations need to be implemented in all pulmonary function test units. A methacholine challenge test will only be performed in the presence of an intermediate pre-test probability for asthma (diagnostic uncertainty), which is an infrequent setting. The most convenient exertional test is the 6-minute walk test that allows the assessment of walking performance, the search for arterial desaturation and the quantification of dyspnoea complaint.

Disruption of the hepcidin/ferroportin regulatory circuitry causes increased pulmonary iron content and restrictive lung disease

All cell types of the lung, including airways, parenchyma and inflammatory cells need iron for metabolic processes. However, they must prevent iron overload which causes cellular damage due to the generation of reactive oxygen species (ROS). The risk for oxidative damage in the lung is exacerbated by its continuous exposure to high oxygen levels making iron detoxification within airway epithelial cells and alveolar macrophages an essential mechanism to prevent lung failure. The aim of our study is to determine the (patho)physiological consequences of unbalanced iron homeostasis in the lung. For this purpose, we analyzed a mouse model with a disruption in the hepcidin/ferroportin circuitry (FPN C326S mice), the regulatory system that controls systemic iron levels. Biochemical and histological analysis of the lung demonstrates that FPN C326S mice exhibit an age dependent increase in pulmonary iron content localized in ciliated airway epithelial cells, alveolar macrophages, alveolar type II cells and smooth muscle cells surrounding pulmonary arteries. Increased pulmonary iron levels correlate with an increase in ROS-mediated lipid peroxidation, suggesting that iron-mediated oxidative stress could contribute to the pathogenesis of lung diseases. To investigate this hypothesis, we performed measurements of lung function and blood oxygen saturation. These analyses revealed signs of restrictive lung disease in FPN C326S mice, with a decrease in total lung capacity and lung compliance. Interestingly, when compared with wild-type littermates, FPN C326S mice present a significant reduction in blood oxygen saturation. Experiments are ongoing to better understand the development of restrictive lung disease and decreased blood oxygen saturation. *Presenting author

Amiodarone-Induced Pulmonary Toxicity Mimicking Metastatic Lung Disease: Case Report

Amiodarone is an antiarrhythmic drug that is commonly used for the treatment of ventricular and supraventricular arrhythmias. It is an iodine-containing compound, and has a tendency to accumulate in certain organs, including in the lungs. We describe a case of amiodarone induced pulmonary toxicity with concurrent lung cancer which demonstrated good treatment response. A sixty nine-year old male smoker presented to our emergency department with a four-month history of progressive dyspnea, cough and 5 kilogram weight loss. Chest x-ray at admission showed enlarged heart shadow and prominent hilum bilaterally; CT revealed ground glass opacities in right lung and enlarged mediastinal lymph nodes. His past medical history was significant for dilated myocardiopathy and atrial fibrillation (for which he had been taking amiodarone for 5 years). Radiological findings, decrease in total lung capacity (TLC=84%), decrease in lung diffusing capacity (DLCOc=73%), and corneal epithelial opacities suggested amiodarone-induced pulmonary toxicity (APT) and/or advanced malignant disease. Amiodarone was eliminated from his medication profile due to suspicion of drug toxicity. The patient’s clinical condition promptly improved, and chest x-ray performed after 7 days showed corresponding improvement. Subsequent bronchoscopy included a transbronchial biopsy which revealed lung adenocarcinoma. The patient’s presumed APT was treated with methylprednisolone 40mg IV daily during the first two weeks, and subsequently with prednisone 20 mg/day orally for two months. One month after steroid therapy (and prior to chemotherapy) both lungs demonstrated radiographic improvement. Treatment response to chemotherapy was successful, with good performance status (ECOG1) after 10 months. This case with comorbid APT and lung cancer illustrates the importance of diligence in developing differential diagnoses for pulmonary infiltrates. Chest physicians should take care to remember that amiodarone induced pulmonary toxicity (APT) can sometimes mimic disseminated lung malignancy.

Airway function in adults with mild-to-moderate scoliosis treated in adolescence with specific physical exercises. An ongoing, case-control study

BackgroundScoliosis can lead to a decrease in total lung capacity(TLC) and alterations in maximal flow volume curves,associated with structural defo rmities and curve magni-tude, but also with chronicity of the problem and respira-tory muscle inefficiency [1-4]. However, evidenceconfirming the assumption of beneficial, long lasting influ-ence of scoliosis specific exercise on respiratory function islacking.PurposeWe aimed to analyze respiratory function in adults withhistory of participation in a scoliosis specific exerciseprogram, in comparison to normative values and to age-matched subjects, with reference to confounders: smokingand physical activity.Materials and methodsMaximal flow-volume curves, ventilatory parameters(vital capacity - VC, forced VC in exertion and in inser-tion = FVCin and FVCex) and TLC values were analyzedin 25 adults (22 females), who attended in adolescence(from 1984 to 1995, at initial age of 11 - 13) the Centreof Corrective and Compensatory Gymnastics, Bielsko Biala, Poland. The WHO General Physical Activity Ques-tionnaire was also completed. The non-parametric rangKruskal-Wallis ANOVA was performed among sub-groups with moderate and mild scoliosis (>40° Cobb,n=3; 25-39°, n=2; 10-24°, n=20, respectively) and com-pared to 17 age matched normal controls (11 females).ResultsGenerally, scoliotic subjects did not differ significantlyfrom controls and normal values. However, FVCin wasbelow normal values (x=86.4% in 10-24° Cobb), VC andTLC means differed nonsignificantly (p=.070 andp=.074, respectively).ConclusionIn general, the results suggest satisfactory lung function-ing, but FVCin analysis indicates inspiratory inefficiency,regardless severity of the deformation.

Alveolar concentration of nitric oxide predicts pulmonary function deterioration in scleroderma

BackgroundRespiratory failure is a life-threatening and unpredictable complication of systemic sclerosis (SSc). A study was undertaken to assess the value of alveolar nitric oxide (NO) in predicting the risk of...

Grading the Severity of Obstruction in Mixed Obstructive-Restrictive Lung Disease

The severity of obstructive pulmonary disease is determined by the FEV(1) % predicted based on the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. In patients with coexisting restrictive lung disease, the decrease in FEV(1) can overestimate the degree of obstruction. We hypothesize that adjusting the FEV(1) for the decrease in total lung capacity (TLC) results in a more appropriate grading of the severity of obstruction. We examined a large pulmonary function test database and identified patients with both restrictive (TLC < 80% predicted) and obstructive (FEV(1)/FVC < the lower limit of normal) lung disease. FEV(1) % predicted was adjusted for the degree of restriction by dividing it by TLC % predicted. We compared the distribution of severity grading between adjusted and unadjusted values according to ATS/ERS criteria and determined how the distribution of severity would change based on asthma and COPD guidelines. We identified 199 patients with coexisting restrictive and obstructive lung disease. By ATS/ERS grading, the unadjusted data categorized 76% of patients as having severe or very severe obstruction and 11% as having mild or moderate obstruction. The adjusted data classified 33% with severe or very severe obstruction and 44% with mild or moderate obstruction. Of the corrected values, 83% resulted in a change to less severe obstruction by ATS/ERS guidelines, and 44% and 70% of patients, respectively, would be reclassified as having less severe obstruction by current asthma and COPD guidelines. This method results in a more appropriate distribution of severity of obstruction, which should lead to more accurate treatment of obstruction in these patients.

Do asbestos-related pleural plaques on HRCT scans cause restrictive impairment in the absence of pulmonary fibrosis?

BackgroundIt is uncertain whether isolated pleural plaques cause functional impairment.ObjectiveTo analyse the relationship between isolated pleural plaques confirmed by CT scanning and lung function in subjects with occupational exposure to...

Obesity, obstructive sleep apnoea, and diabetes mellitus: anaesthetic implications

Obesity is an epidemic in much of the Western World. The extent of this problem, combined with the increasing preference for ambulatory surgical procedures, has produced a difficult situation for many anaesthesiologists. Even the simplest anaesthetic procedures can become very complicated and potentially difficult in this population. Although there are numerous complications associated with obesity, perhaps obstructive sleep apnoea (OSA) and diabetes mellitus are among the more significant. Patients with OSA are often not ideal candidates for certain day-case procedures, but many outpatient procedures can be performed on patients with OSA as long as attention is paid to anaesthetic technique. Diabetic patients are prone to numerous complications in the perioperative period, including cardiac problems, but with careful management, they are able to undergo day-case surgical procedures safely.

Effects of a DNA vaccine in an animal model of Alternaria alternata sensitivity

Sensitivity to the fungus Alternaria is associated with asthma persistence and severity. Current therapeutic options for treating Alternaria-induced airway inflammation are limited. In this study, Brown Norway rats are used to study the effectiveness of a DNA-based vaccine delivered to the airway in attenuating the response to a major Alternaria allergen, rAlt a 2. Compared to untreated sensitized animals, or animals receiving an “out-of-frame” DNA-based vaccine, animals treated with “in-frame” DNA vaccine showed an attenuation in specific IgE antibody titers to rAlt a 2, an increase in IgG 2b (a Th1 response), a reduction in spontaneous IL-13 release by peribronchial lymph node cell suspensions, and an attenuation in the decrease in total lung capacity 72 h post-allergen challenge. Further, histopathologic examination of the lung tissues revealed reduced pulmonary inflammation post-allergen challenge in the DNA-vaccine-treated compared to sensitized, untreated animals. We conclude that a DNA-based vaccine delivered to the airway significantly influences the immunologic, pulmonary physiologic, and histological alterations induced by challenge with a major Alternaria allergen, rAlt a 2, in sensitized animals.

Restrictive impairment in patients with asthma

Patients with asthma have intermittent or persistent airflow obstruction, most often manifested spirometrically by reduced forced expiratory volume in 1s (FEV(1)) and FEV(1)/vital capacity (VC) ratio. In some patients, the VC may be reduced by air trapping, with an increase in functional residual capacity (FRC) and residual volume (RV) (pseudorestriction). We have reported 12 asthmatic patients with reduced VC and no increase in RV, i.e., a true restrictive impairment [Gill et al. True restrictive impairment in bronchial asthma. Am J Respir Crit Care Med 1999:159:A652]. To confirm previous observations of true restrictive impairment (not attributable to air trapping) in patients with asthma, and to estimate its frequency in an asthmatic population. Review of pulmonary function tests and clinical records of all post-pubertal patients diagnosed as asthma between January 2000 and September 2003 in a 184 bed inner city teaching hospital in Jamaica, Queens, New York. The clinical diagnosis of asthma was accepted when one or more of the following pulmonary function criteria were met: Positive bronchodilator response (BD), positive methacholine, repeated variability in spirometric values. Restriction was defined as decrease in total lung capacity (TLC) or decrease in VC with no increase in functional residual capacity (FRC) plus normal or high FEV(1)/FVC ratio. Patients with any clinical finding consistent with restriction, including a decreased diffusing capacity (DL) or obesity (BMI >30) were excluded. A total of 100 of 413 (24%) patients with asthma had restriction; 21 of these met all exclusions (including DL and BMI) and 11 (of 46) patients with an increased BMI and normal DL normalized their FVC on BD therapy, demonstrating that their pre-BD restrictive impairment could not be attributed to obesity. Plethysmographic FRC was measured in 81 of the 100 patients with restriction and was increased in only seven. True restrictive impairment was noted in at least 32 of 413 asthmatics (8%), consistent with previous observations in asthma and reactive airways dysfunction syndrome. This finding is not widely recognized and should not preclude the diagnosis of asthma, BD testing or appropriate therapy for asthma.

The Relationship Between Lung Function and Health-Related Quality of Life in Patients With Generalized Myasthenia Gravis

To study lung function abnormalities and health-related quality of life (HRQL) in a group of patients diagnosed with generalized myasthenia gravis, and to analyze the relationship between these 2 sets of variables. In a prospective study of 20 patients diagnosed with generalized myasthenia gravis, the following parameters were measured: spirometry, static lung volumes, breathing pattern, maximal respiratory pressures, and maximum voluntary ventilation. HRQL was assessed using the 36-item short form general health questionnaire (SF-36). The mean (SD) age of the patients was 64 (11) years. Patients were classified into 2 groups depending on whether they had IIa (12 patients) or IIb (8 patients) type disease. A small decrease in total lung capacity (86%) and slight reductions in maximal inspiratory pressure (88%) and maximum voluntary ventilation (63% in group IIb) were observed. The HRQL domains most affected were those related to physical activity and self-perceived health status in all groups, although women were more affected. The scores relating to vitality and physical activity were found to be significantly associated with forced vital capacity and lung volumes. Tidal volume was associated with maximal inspiratory and expiratory pressures, inspiratory capacity, and maximum voluntary ventilation. The respiratory rate to tidal volume ratio was inversely associated with the first three of these variables. A very slight restrictive pattern and a reduction in inspiratory muscle strength were observed. The HRQL domains most affected were those related to physical activity and the patients' self-perceived health status. The weakness of the respiratory muscles contributes to the abnormalities observed in lung function and to the deterioration of health-related quality of life.

Systemic and pulmonary effects of fluticasone administered through a metered-dose inhaler in rats

Metered-dose inhalers (MDIs) are convenient, simple, inexpensive, and reproducible devices for administering aerosolized drugs through the pulmonary route, but methods have not been available for use of these devices in small animals. We sought to test the efficacy of delivery of fluticasone through an MDI to rats with a rodent-adapted spacer chamber and to compare this treatment with systemic dexamethasone for the acute pulmonary allergic inflammatory response. Changes in body and thymus weights were used as indicators for systemic steroid effects. Rats were sensitized to ragweed pollen extract 2 weeks before the experiment, and pulmonary allergic responses were evaluated 48 hours after a single aerosolized antigen challenge on the basis of bronchoalveolar leukocytes, lung tissue sections, total lung capacity, and forced expiratory volumes. Inhaled fluticasone caused dose-related systemic effects, indicating successful pulmonary drug delivery. Inhaled fluticasone was more effective than placebo but less effective than systemic dexamethasone in attenuating the increase in lung eosinophils and inflammatory infiltrates and the decrease in total lung capacity associated with the allergic inflammatory response. Inhaled fluticasone prevented airway obstruction and proximal inflammation, as did dexamethasone, but it appeared to have less effect in areas of lung served by the most distal airways. This is an effective method for use of MDIs to deliver inhaled drugs to small laboratory animals, and it should be valuable for investigations of treatment effects, as well as for in vivo testing of delivery devices.

Lung function impairment in relation to asbestos-induced pleural lesions with reference to the extent of the lesions and the initial parenchymal fibrosis.

The study focused on the effect of pleural lesions on the lung function of asbestos-exposed workers. A clinical check-up, chest radiography, high-resolution computed tomography (HRCT), and lung function testing were performed on 162 asbestos-exposed workers without any sign of parenchymal fibrosis on their chest radiographs. According to the HRCT scans, two subgroups were delineated, 97 subjects with pleural lesions and 65 referents without pleural lesions. Four categories of pleural lesions were specified according to the extent. Parenchymal changes, if identified on the HRCT scans, were recorded. The radiographic sensitivity and specificity for pleural lesion detection when compared with that of HRCT were 64.9% and 98.5%, respectively. The HRCT scans showed parenchymal abnormalities in 46.3% of the participants, more frequently in those with pleural lesions (67.0% versus 15.4%, P<0.0001). After the effect of parenchymal fibrosis was taken into account, pleural lesions were found to have a significant effect on the decrease in total lung capacity, forced vital capacity, and forced expiratory volume in 1 second, if being classified into category 2 or higher. Pleural lesions proved to have a negative effect on lung function, depending on their extent. The effect of the initial parenchymal fibrosis detectable in the HRCT scans only was also significant. A normal chest radiograph does not exclude the presence of pleural lesions or initial parenchymal fibrosis, with a possible negative effect on lung function.

Late pulmonary effects in favorable stage I and IIA Hodgkin's disease treated with radiotherapy alone.

Radiotherapy (RT) in patients with favorable-stage Hodgkin's disease can induce clinical and subclinical evidence of pulmonary damage lasting over the years. In this study, we monitored 36 patients with stage IA-IIA Hodgkin's disease treated with subtotal nodal RT. The planned dose of RT was 40 Gy to 44 Gy to the involved areas and 36 Gy to the adjacent uninvolved areas. Pulmonary function was evaluated by chest radiograph, spirometric parameters, arterial blood gas analysis, and single-breath CO transfer factor (DLCO). The tests were performed before and at the end of irradiation, and during the follow-up 1 and 3 to 5 years after the treatment. At the end of RT, we found a significant decrease of total lung capacity, vital capacity, forced expiratory volume in 1 second, residual volume, and DLCO. Spirometric parameters improved during the follow-up period, whereas the decline of DLCO (-6.4%) was persistent. No correlation was found between mantle RT dose and DLCO changes. Four patients showed a decline of DLCO of >20% from pretreatment values but only one was symptomatic. Our study confirms that RT induces a pulmonary-restrictive disease at a subclinical level that seems to be reversible in the majority of patients.

Lung volume reduction for emphysema and the Canadian Lung Volume Reduction Surgery (CLVR) Project.

To review the literature on the surgical treatment of emphysema and to present preliminary results from a pilot study of lung volume reduction (LVR) surgery. Case series of consecutive patients referred for LVR surgery. Outcomes were quality of life, pulmonary function and exercise capacity. Two university-affiliated hospitals in Ontario. Patients between the ages of 40 and 75 years with emphysema who had severe airflow limitation, hyperinflation of the lungs and impaired quality of life. Bilateral reductions with multiple wedge resections of the lung using a linear stapling device with bovine pericardial buttressing were completed via a median sternotomy. Of 50 patients referred, 24 underwent LVR surgery. Mean age of the cohort was 63 years. Operative 30-day or in hospital mortality was 8%. Two other patients (8%) died from respiratory failure after LVR within the first year. Postoperative complications included prolonged air leaks (six of 24), tracheobronchitis (five of 24), mechanical ventilation (four of 24) and pneumonia (three of 24). Mean length of stay was 18 days (median 12 days). At one year, there was a sustained decrease in total lung capacity from 133% to 123% predicted. There were improvements in forced expiratory volume in 1 s, from 22% of predicted preoperatively to 32% postoperatively, and in 6 min walk performance, from 345 to 381 m. Improvements were also noted in the quality of life assessments. Preliminary results suggest that LVR surgery is feasible and may improve the patient's quality of life, pulmonary function and exercise capacity. A randomized clinical trial comparing LVR plus the best medical management with the best medical management alone is currently underway to determine the effectiveness of LVR.

Lung volume reduction surgery for emphysema.

Lung volume reduction surgery (LVRS) is performed to alleviate dyspnoea of selected patients with severe pulmonary emphysema and to improve their pulmonary function, performance in daily activity and quality of life. By resection of destroyed lung areas the achievable improvements in function may consist of: 1) a reduction in hyperinflation resulting in amelioration of diaphragm and chest wall mechanics; 2) an increase of elastic recoil pressure, thereby augmenting expiratory flow rates; and 3) possibly an improvement in gas exchange. Meticulous selection of suitable patients, refinements in operative techniques, anaesthesiological and postoperative management has lowered perioperative mortality to less than 5% in groups who are experienced with this type of procedure. The best functional results are achieved by bilateral resection, which can either be performed by median sternotomy or by video-assisted thoracoscopy (VAT). The average increase in forced expiratory volume in one second (FEV1), obtained by bilateral resection in patients already receiving optimal medical therapy ranges 32-93%, and the reduction in hyperinflation, assessed by a decrease in total lung capacity ranges 15-20%. These favourable improvements have been reported to last in most of the patients for at least one year.

Correlation between pulmonary fibrosis and the lung pressure-volume curve.

The severity of pulmonary fibrosis is the main prognostic factor for survival of patients with interstitial lung diseases (ILD). Unfortunately, lung biopsy, which is the best method to assess fibrosis quantitatively, is done only once during the evolution of the disease. In this study we analyzed the relationship between the degree of fibrosis and the exponential constant k, derived from the lung pressure-volume curve (LPVC) in 33 patients with chronic ILD, 19 with pigeon breeder's disease (PBD), and 14 with idiopathic pulmonary fibrosis (IPF). Pulmonary function tests, including the LPVC, were obtained before biopsy. A semiquantitative histologic assessment of the severity of fibrosis was performed on lung tissues. All patients showed a decrease of total lung capacity, residual volume, compliance, and Pao2. The mean value of the constant k was 0.08 +/- 0.06. When expressed as a percent of normal values, 25 patients exhibited values of k lower than 70% of predicted; of the remaining 8 patients whose values were above 70% of predicted, 7 had PBD and only one IPF. On morphologic analysis, 19 patients displayed more than 50% fibrosis. No significant correlations were found between the extent of the lesion or severity of lung fibrosis and the conventional pulmonary function tests. By contrast, a moderate but significant correlation was found between k and the severity of lung fibrosis (r = -0.38, p < 0.05). These findings show that the shape of the LPVC, represented by the constant k, predicts the degree of lung fibrosis and could be useful in the clinical assessment and follow-up of patients with ILD.

Respiratory function in systemic lupus erythematosus: relation with activity and severity

The objective of this study was to examine the relation between respiratory function tests, disease activity and disease severity in ambulatory patients with systemic lupus erythematosus (SLE) who did not present with overt respiratory problems. Lung volumes, maximal expiratory flows at 50% and 25% of vital capacity (MEF50 and MEF25), bronchial threshold to methacholine (PD15FEV1), transfer factor CO (KCO) were measured in 24 consecutive SLE outpatients (22 women, age 41 +/- 14.8 years) and in 24 healthy controls matched for age and sex. In SLE patients alveolar-arterial oxygen gradient (AaO2) was also measured. Disease activity was assessed by European Consensus Lupus Activity Measurement (ECLAM) scoring system and disease severity by Lupus Severity of Disease Index. In comparison to controls SLE patients showed a significant decrease of total lung capacity (TLC) (91.7 +/- 16.5 vs 102.7 +/- 12.9% predicted, P < 0.01), MEF25 (58.4 +/- 25.2 vs 73.5 +/- 19.5% predicted, P < 0.005) PD15FEV1 (2164 +/- 1122 vs 4230 +/- 1014 micrograms methacholine, P < 0.0001) and KCO (77.1 +/- 20.5 vs 96.3 +/- 12.4% predicted, P < 0.001). AaO2 (mean value 13.2 +/- 8.4) was abnormally high (> 20 mmHg) in 12 patients. The ECLAM score of activity was inversely related with KCO (r = 0.48, P < 0.02). The severity index was significantly related with FEV1/VC ratio (r = 0.43, P < 0.05), MEF50 (r = 0.51, P < 0.01), MEF25 (r = 0.40, P < 0.05) and PD15FEV1 (r = 0.51, P < 0.01). In eight patients, evaluated also after treatment intensification, there was a significant increase in KCO (from 71.8 +/- 24.7 to 84.9 +/- 22.3% predicted, P < 0.01) along with a decrease in ECLAM score (from 3.0 +/- 1.34 to 0.69 +/- 0.75, P < 0.01). The relation between disease activity and KCO suggests a relation between systemic and alveolar inflammation whereas the relation between severity index, airway patency and reactivity indices suggests a cumulative damage to the airways in SLE patients, even in the absence of overt respiratory manifestations.

Ozone-Induced Pulmonary Functional, Pathological, and Biochemical Changes in Normal and Vitamin C-Deficient Guinea Pigs

Ozone-Induced Pulmonary Functional, Pathological, and Biochemical Changes in Normal and Vitamin C-Deficient Guinea Pigs. Kodavanti, U. P., Hatch, G. E., Starcher, B., Giri, S. N., Winsett, D., and Costa, D. L. (1995). Fundam. Appl. Toxicol. 24, 154-164.Since Vitamin C (ascorbate, AH2) is an important airway antioxidant and is an essential component of tissue repair, and since acute (4 hr) O3 toxicity is enhanced by AH2 deficiency, we hypothesized that longer-term O3 effects might also be increased. Female Hartley guinea pigs (260-330 g) were fed either and AH2-sufficient or an AH2-deficient diet 1 week prior to exposure, and were maintained on their respective diets during 1 week of continuous exposure to O3 (0, 0.2, 0.4, and 0.8 ppm, 23 hr/day), and during 1 week postexposure recovery in clean air. The AH2-deficient diet caused lung AH2 to drop to about 30% of control in 1 week, and to below 10% by the end of exposure and recovery. Body weight gains during exposure were decreased in the 0.8 ppm O3 group, while the AH2 deficiency began to affect body weights only during recovery. O3 caused a concentration-dependent decrease in total lung capacity, vital capacity, carbon monoxide diffusing capacity, nitrogen washout, and static compliance, while increasing forced expiratory flow rates and residual or end-expiratory volume (suggestive of pulmonary gas-trapping). The lung/body weight ratio and fixed lung displacement volume were also increased in O3-exposed animals. Lung pathology consisted of mononuclear cell and neutrophil infiltration, airway as well as alveolar epithelial cell hyperplasia, and general decrease in epithelial cell cytoplasm. Thickening of the interstitium and an apparent increase in collagen staining were seen at the terminal bronchiolar regions. Some of these effects were marginally exacerbated in AH2-deficient guinea pigs. One week postexposure to air reversed all O3-induced abnormalities, irrespective of AH3 deficiency. Whole lung hydroxyproline and desmosine were not changed at any time by either O3 or AH2 deficiency. Measurement of lung prolyl hydroxylase activity suggested that AH2 deficiency as well as O3 exposure may have increased the tissue levels of this enzyme. The lack of a significant increase in toxicity with the longer-term exposure scenario suggests that AH2 has minimal influence on other compensatory mechanisms developed over time.