Comparative analysis of different scintigraphic approaches to assess pulmonary ventilation.

A study was carried out to investigate the predictive value of 81-metastable-krypton (81mKr) distribution, high-size 99-metastable-technetium (99mTc) aerosol deposition and low-size 99mTc aerosol (Technegas) deposition on the pulmonary ventilation evaluated by 133-xenon (133Xe) lung scintigraphy, and to assess the correlation between the 81mKr distribution, the 99mTc aerosols deposition, and the respiratory parameters of patients with chronic obstructive pulmonary disease (COPD). Twenty COPD patients were included. The 81mKr, 133Xe, and 99mTc aerosol lung scintigraphies were successively carried out. The 81mKr distribution and 99mTc deposition were compared to the 133Xe distribution at equilibrium and to the 133Xe clearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81mKr and Technegas lung scintigraphies to detect alterations in ventilation revealed by 133Xe were defined. The 81mKr distribution and 99mTc deposition according to respiratory parameters were described using a principal component analysis. Compared to 133Xe distribution, a significantly higher distribution of 81mKr in the upper parts of the lungs in the more severe patients (p = 0.05), a significantly higher deposition of Technegas in the lower parts of the lungs (p = 0.0008), and a significantly higher deposition in the central parts of the high-size 99mTc aerosol were observed (p = 0.0001). The PPV and the NPV were, respectively, 0.54 and 0.58 for 81mKr and 0.54 and 0.55 for Technegas. There was a significant negative correlation between 81mKr distribution and 133Xe clearance (p = 0.0001) between Technegas deposition and 133Xe clearance (p = 0.0007), and between 99mTc diethylene-triamino-penta-acetate (DTPA) deposition and 133Xe clearance (p = 0.001). Both the 81mKr peripheral distribution and Technegas peripheral deposition correlated negatively with increased obstruction, as measured by forced expiratory volume in 1 sec (FEV1). Peripheral deposition of the high-size 99mTc aerosol deposition correlated with the inspiration/expiration time ratio. In conclusion, 81mKr and 99mTc aerosols' lung scintigraphies do not reflect exactly the pulmonary ventilation as measured by 133Xe scintigraphy.

Relationship between abnormalities on high-resolution CT and pulmonary function in systemic sclerosis.

STUDY OBJECTIVES: To determine the predictive value of abnormalities on high-resolution CT (HRCT) on pulmonary disease in systemic sclerosis. PATIENTS: Fifty-two patients suffering from systemic sclerosis. DESIGN: Pulmonary disease was defined by pulmonary function test abnormalities, ie, total lung capacity (TLC) <80% of predicted value and/or diffusion of carbon monoxide (DLCO) <75% of predicted value, without any pulmonary event other than systemic sclerosis in the medical history. Patients were divided in two groups, group A with pulmonary disease (29 patients) and group B without pulmonary disease (23 patients). HRCT abnormalities were scored on whole lungs. A decision matrix was constructed to determine sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates. A receiver operating characteristic curve was constructed to determine the best compromise between sensitivity and specificity. RESULTS: HRCT total scores were higher in group A (9.0+/-4.3) than in group B (5.0+/-2.8) (p < 0.001) and they correlated with TLC (r =-0.39, p < 0.005) and DLCO (r = -0.50, p < 0.0002). An HRCT score of 7 corresponded to the best compromise between sensitivity (0.60) and specificity (0.83), with a positive predictive value of 0.82. Taking into account a value of 10 for the HRCT score increased specificity to 1 but decreased sensitivity to 0.41. CONCLUSION: A minimum score of 7 would be required to consider HRCT abnormalities in systemic sclerosis as predictive of pulmonary disease. An HRCT score of 10 makes it possible to establish the diagnosis of lung involvement severe enough to impair pulmonary function.

Characteristics of EPI-hNE4 aerosol: a new elastase inhibitor for treatment of cystic fibrosis.

The purpose of this study was to define nebulization conditions providing delivery of aerosols of EPI-hNE4, an inhibitor of human neutrophil elastase (HNE). EPI-hNE4 was nebulized with Pari LC Star and tested at three concentrations (2.5, 5, and 10 mg/mL). The inhaled mass was measured over 15 min. Particle size distribution was measured by cascade impaction. The effect was also tested of mixing EPI-hNE4 with a (99m)Tc human serum albumin (HSA) tracer on the aerodynamic properties of the aerosol. The inhibitory activity of EPI-hNE4 after nebulization was assessed on purified HNE. The inhaled mass was 32.3 +/- 3.5% (mean +/- SD) after 10 min and 44.2 +/- 3.8% (mean +/- SD) after 15 min. Mass median aerodynamic diameter ranged between 1.2 and 1.8 microm. The (99m)Tc HSA EPI-hNE4 aerosol was similar in terms of particle size distribution (y = 1.0338x - 0.003, r = 0.83). (99m)Tc activity was predictive of EPI-hNE4 mass distribution (y = 1.0278x - 1.6991, r = 0.89). The inhibitory capacity of aerosolized samples remained unchanged after up to 10 min of nebulization. EPI-hNE4 can be nebulized efficiently without decrease in its activity. Mixing this inhibitor with (99m)Tc HSA should allow quantification of its deposition in CF patients.

Validation of laser diffraction method as a substitute for cascade impaction in the European Project for a Nebulizer Standard.

The project for a European standard testing procedure to characterize nebulizers in terms of particle size distribution has been based on using the Andersen-Marple personal cascade impactor model 298 (A-MPCI) with a sodium fluoride reference solution. In the present study methods based on laser diffraction (Mastersizer-X) and time-of-flight (TOF)(APS) and another cascade impactor (GS1-CI) were compared with the A-MPCI. Two types of nebulizer (Pari LC+ and Microneb) were tested with all apparatuses, and a third type of nebulizer (NL9) was tested with the A-MPCI and Mastersizer-X. Nebulizers were charged with a solution of sodium fluoride in conditions reproducing the European Committee for Normalization (CEN) protocol. There was no difference between the Mastersizer-X and the A-MPCI or between the GS1-CI and the A-MPCI in terms of mass median aerodynamic diameter (MMAD). Comparison between the APS and the A-MPCI showed a significant difference with the Microneb. The geometric standard deviations (GSD) obtained with the A-MPCI were on average 10% greater than GSD obtained with the other apparatuses, but the differences were not statistically significant. We conclude that laser diffraction can be used for particle size distribution in the context of the European standard, and that the Mastersizer-X is particularly interesting for industrial practice in view of its simplicity and robustness.

Aerosols and anti-infectious agents.

Anti-infectious agents such as pentamidine, antibiotics (mainly colistine and aminoglycosides), and amphotericin B can be administered by aerosol. Apart from pentamidine and Tobi, this route of administration is not officially approved and it constitutes an empirical approach, which has benefited from recent research summarized hereafter. The most fundamental question is related to the potentially deleterious effects of nebulization processes, especially ultrasound, on the anti-infectious properties of the drugs. Colimycin, which was chosen as a reference because its polypeptide structure makes it unstable a priori, proved to be resistant to high frequency ultrasound, which is encouraging for other molecules such as aminoglycosides or betalactamins. The nebulizer characteristics also have to be taken into account. An aerosol can be produced from an amphotericin B suspension and from colistine using both an ultrasonic nebulizer and a jet nebulizer. Differentiating between good and bad nebulizers is not dependent upon the physical process involved to nebulize the drug, but on the intrinsic characteristics of the device and its performance with a known drug. The inhaled mass of an aerosol in the respirable range must be high and dosimetric nebulizers represent significant progress. Finally, administration of anti-infectious aerosols requires a new pharmacological approach to monitor treatment, and urinary assays are promising for this purpose.

[Hypercapnic status asthmaticus. Rapid reversibility of hypercapnia under medical treatment]. / Etat de mal asthmatique hypercapnique. Réversibilité rapide de l'hypercapnie sous traitement médical.

Fifty-four episodes of hypercapnic status asthmaticus (Pa CO2 50 mmHg or more) were treated with intravenous theophylline (6 mg/kg over 30 minutes, then 1 mg/kg/hour), intravenous hydrocortisone hemisuccinate (1 g then 500 mg 4-hourly) rehydration and oxygen therapy at a sufficient rate to obtain a Pa O2 of 80 mmHg or more. As a rule, improvement was rapid with a significant decrease of mean Pa CO2 values from 61 +/- 14 to 44.5 +/- 11.5 mmHg (P less than 0.001) over 2 hours. In only 3 cases was mechanical ventilation necessary. An initially high Pa CO2 value is not an absolute indication of mechanical ventilation. This method remains exceptional and can be avoided in most patients by the emergency medical treatment outlined above.

[Hematopoietic growth factors and anti-infective respiratory defenses]. / Facteurs de croissance hématopoïétiques et défenses anti-infectieuses respiratoires.

Colony-Stimulating Factors (CSFs) are a family of glycoproteins that are required for the proliferation and differentiation of hematopoietic progenitor cells. Among these factors, G-CSF and GM-CSF are principally involved in the production of neutrophils. They have been demonstrated to be effective in correcting neutropenia during cytotoxic chemotherapy or bone marrow transplantations. Beside their hematopoietic action, recent data indicate that G-CSF and GM-CSF also have stimulatory effects on mature neutrophils function. The functional properties of neutrophils that are enhanced by G-CSF and GM-CSF are those related primarily to the host's defense against microorganisms. For Gm-CSF those stimulatory effects also concern the macrophages. Investigations of several animal models of severe bacterial infection and specially pneumonia have indicated that exogenous recombinant G-CSF or GM-CSF can significantly enhance host defenses and improve rates of survival. Trials of recombinant G-CSF in combination with antibiotics for the treatment of severe pneumonia in noneutropenic patients have recently been initiated. First results confirm the good tolerance of recombinant G-CSF. Further prospective studies are required to determine the effectiveness and the conditions of administration of G-CSF and GM-CSF in this indication.

[Atmospheric and respiratory contamination by waste water aerosols]. / Contamination atmosphérique et respiratoire par les aérosols d'eaux résiduaires.

A study was undertaken of the particle size of aerosols, emitted by a treatment plant for urban waste water, by counting the total flora, using and Andersen apparatus. Evidence of significant bacterial contamination was obtained on the perimeter of the installations. Calculations were made on the data obtained using a method to show the number of viable particles deposited at different levels within the pulmonary tree. During the working day approximately 10(4) viable particles, representing 1.5 x 10(6) organisms, products of the common flora of activated sludge were inhaled. Only a small fraction enters the pulmonary acini; the greater part are swallowed or excreted via the nose or on coughing.

[Characterization by isotope method of the performance of the pneumatic nebulizer NL9 Atomizer in the production of colistin, tobramycin and amiloride aerosols]. / Caractérisation par méthode isotopique des performances du nébuliseur pneumatique NL9 Atomisor pour la production d'aérosols de colistine, tobramycine et amiloride.

The objective of this study was to assess the performance of a new pneumatic nebuliser NL9 Atomisor. The performance was assessed in terms of particle distribution, fraction nebulised, fraction inhaled and percentage of particles of a diameter of between 1 and 4 microns for the nebulisation of physiological serum, colistin, tobramycin and amiloride. The solutions were nebulised in the approved formula for their reconstitution as used in the clinic after the addition of sodium pertechnetate. The validity of this indirect isotopic method has been shown before. The nebuliser was coupled, during the nebulisation, to a pump respirator with six settings. The fraction nebulised was defined as the percentage of the volume of the solution which had left the aerosol generator at the end of the nebulisation. The fraction inhaled was defined as a percentage of the volume of the solution which was gathered at the end of the nebulisation on a filter placed in the inspiratory circuit of the aerosol generator. The study of the distribution of aerosol particle sizes was carried out using a cascade impactor at ten stages. Each of these parameters was determined in triplicate for the four solutions studied. The nebulised fraction consisted of between 33.5 and 58.6% (mean 49.7 +/- 8.1%). The inhaled fraction consisted of between 14 and 30.4% (mean 24.5 +/- 5.5) and the duration of nebulisation was between 10 and 20 minutes. The MMAD was between 1.6 microns with tobramycin 3.5 microns with physiological serum.(ABSTRACT TRUNCATED AT 250 WORDS)

[Chronic course of reactive bronchial dysfunction syndrome. Apropos of 6 further cases]. / Evolution chronique du syndrome de dysfonction réactive des bronches. A propos de 6 nouveaux cas.

The reactive airways dysfunction syndrome (RADS) occurs as a persistent bronchial hyper-reactivity with asthmatic-type dyspnoea and occurs after a single and massive inhalation of irritant gases, smoke or vapours, in subjects who had previously had no respiratory disease. We report six cases in patients without any previous asthmatic history or history of atopy who had developed RADS after being exposed to different irritants. The symptoms evolved over 5-84 months after the initial accident. Only moderate airflow obstruction was found, but all subjects had bronchial hyper-reactivity to methacholine. A bronchial biopsy was performed in a patient and this showed moderate sub-epithelial mononuclear inflammatory infiltrate. A specific feature of this syndrome is the facility to inaugurate a susceptibility to asthma after the initial accident and for this to progress of its own accord with secondary aggravation, even in the absence of new exposure to the irritating agent. Its frequency is probably under-estimated because it remains little known in France. It is very important both to recognise and notify inhalational accidents at work to be able, should the nedd arise, to identify the worker and to enable a move to a different job if necessary.

[Evaluation of the mean annual risk of tuberculosis infection in the town of Conakry]. / Evaluation du risque annuel d'infection tuberculeuse au moyen d'une enquête tuberculinique dans la ville de Conakry.

A study of tuberculous disease was carried out in children aged 5 to 13 years old who were first year pupils in primary schools in the town of Conakry (Republic of Guinae) with a view to determining the annual risk of tuberculous infection. In total 4,198 children distributed throughout 15 schools were tested after first looking for BCG vaccination scars. In the sample tested 1,444 children (34.4%) had vaccination scars and 2,754 (65.6%) did not. Amongst the 1,444 children with BCG scars, 1,367 (94.7%) were reviewed 72 hours after one unit of tuberculin RT 23 to have the skin reaction RDI read. Amongst these 210 (15.4%) had an area of induration greater than 6 m.m. diameter. Amongst 2,754 children who did not have BCG scars 2,655 (96.4%) were reviewed for the reading of the IDR: 330 children (12.8%) had an area of induration greater than 6 m.m. diameter. The percentage of children with an IDR greater than 6 m.m. as well as the mean diameter of induration was significantly greater in the group with a vaccination scar. The age of the children influenced the size of the induration. A factorial analysis revealed at the same time an age factor and a significant scar factor. Calculations from the prevalence of areas of induration with diameter greater than 6 m.m. in non-vaccinated children revealed an annual risk of infection of 1.52. A number of cases of pulmonary tuberculosis with positive microscopy in Conakry town is estimated at 90 per 100,000 inhabitants.

[Bronchial provocation tests in 59 asthmatic children. Comparison with skin tests and specific serum allergens]. / Epreuves de provocation bronchique chez 59 enfants asthmatiques. Comparaison avec les tests cutanés et les réagines sériques spécifiques.

Fifty nine asthmatic children were assessed by skin tests (prick-tests) (TC), specific serum IgE level (R.A.S.T.) and bronchial provocation tests (TPB) with house dust, mites, grass pollen, animal scales and moulds. The concordance of the skin and R.A.S.T. tests with the provocation test, chosen for reference and their diagnostic value was analysed using decision matrices. There was a significant connection between the results of the three tests. The concordance level was only moderate not passing 68%. By comparison to TPB there were numerous false positive Prick-tests and false negative R.A.S.T. The negative predictive value of TC was satisfactory. The most discriminatory threshold for the positive R.A.S.T. was the class 3 response. These results allow the following diagnostic possibilities to be considered. For a common allergen a negative prick-test (TC) would lead to the end of the investigations except for certain particular cases; for an allergen of low prevalence a positive TC should be taken into account, and completing this with RAST and TPB. One could envisage a reduction in the number of TPB and R.A.S.T. performed, reserving them for cases where a discordance between the clinical history and the T.C.

[Anti-infective aerosols]. / Les anti-infectieux en aérosols.

Anti-infectious agents such as pentamidine, antibiotics (mainly colistine and aminoglycosides) and amphotericin B can be administered by aerosol. This route of administration is not officially approved and it constitutes an empirical approach which has benefited from recent research which is summarized hereafter. The most fundamental question is related to the potentially deleterious effects of nebulization processes, especially ultrasound, on the anti infectious properties of the drugs. Colimycin, which was chosen as a reference because its polypeptide structure makes it unstable a priori, proved to be resistant to high frequency ultrasound, which is encouraging for other molecules such as aminoglycosides or betalactamins. The nebulizer characteristics have also to be taken into account. An aerosol can be produced from an amphotericin B suspension and from colistine using both an ultrasonic nebulizer and a jet nebulizer. Distinction between good and bad nebulizers does not depend upon the physical process involved to nebulize the drug, but on the intrinsic characteristics of the device and its performance with a known drug. The inhaled mass of an aerosol in the respirable range must be high and dosimetric nebulizers represent a significant progress. Finally, adminnistration of anti infectious aerosols requires a new pharmacological approach to monitor treatment and urinary assays are promising.

[Dyspnea and morphine aerosols in the palliative care of lung cancer]. / Dyspnée et aérosols de morphine dans les soins palliatifs du cancer broncho-pulmonaire.

OBJECTIVE: To evaluate the effectiveness of morphine aerosols in the treatment of dyspnoea in the palliative care of patients with lung cancer. MATERIALS AND METHODS: During a randomised, double blind, cross-over study 12 patients receiving palliative care for lung cancer and suffering from dyspnoea despite conventional treatments were given, for two periods of 48 hours separated by a 24 hour wash-out period, 4 mls of morphine sulphate and 4 mls of normal saline 4 hourly by a jet nebuliser. Before and after each nebulisation respiratory rate and capillary oxygen saturation were measured and dyspnoea was quantified with the aid of a visual analogue scale by the patient and various other observers (doctors, students, nurses, care assistants and physiotherapists). RESULTS: The aerosols of normal saline and morphine produced the same improvements in the dyspnoea scores independently of the mass nebulised. Furthermore the nebulisations did not produce any significant change in respiratory rate or oxygen saturation. CONCLUSION: The fact that both aerosols lead to a similar improvement in dyspnoea scores suggests that humidification of the airways rather than a pharmacological action may be beneficial in the treatment of dyspnoea in terminally ill patients.

[Strategy for early diagnosis of lung involvement in systemic scleroderma]. / Stratégie pour le diagnostic précoce de l'atteinte pulmonaire dans la sclérodermie systémique.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by accumulation of collagen in affected organs, mainly the skin and the lungs, associated with abnormalities of the arterioles and capillaries. There are two types of pulmonary involvement, which influence long term prognosis: infiltration of the lungs and/or pulmonary artery hypertension. Full investigations into possible lung involvement must be performed systematically when SSc is diagnosed and during follow-up. The double pathophysiology sometimes makes diagnosis difficult but it must be made as early as possible in order to decide on the optimal treatment. The aim of this study was to evaluate the usual explorations and to propose biological markers to identify patients requiring more detailed lung investigations, in order to establish a diagnostic approach to treatment and follow-up patients with SSc.

[Serum procalcitonin and respiratory tract infections]. / Procalcitonine sérique et pathologie infectieuse respiratoire.

The aim of our study was to evaluate the prognostic value of serum procalcitonine (PCT) assay in adult respiratory infections. Forty-nine patients admitted with pleurisy, community-acquired pneumonia, tuberculosis, infection were included in this prospective study. PCT was assayed on admission and discharge. Biological and clinical parameters of gravity were also evaluated. Twenty patients had elevated PCT of more than 0.50 ng/ml. In 29 patients, PCT was undetectable. The serum PCT level was normal in the patients with tuberculosis, infection, pneumocytosis. PCT did not correlate with the biological and clinical markers of the disease severity but the evolution of PCT correlated with the evolution of C-reactive-protein (r = 0.58, p < 0.05). PCT seems to be an early marker of the evolution of respiratory infections, but it does not help to establish prognosis. Further studies are necessary to assess the potential value of PCT in more severe respiratory infections requiring assisted ventilation.

[Measurement of peak expiratory flow and altitude]. / Mesure du débit de pointe et altitude.

Readings of peak-expiratory flow rate (PEFR) in twelve healthy alpinists at sea level (Lima) and at 3800 m (Yanganugo) show a significant slight fall with altitude (p less than 0.05). This study corroborates previous reports (Singh et al., 1969; Stockley et al., 1979). However, Forster (1983) taking in account the effect of air density on the functioning of peak-flow meter suggested that actual PEFR increases slightly with altitude. In the present study, corrected data show an increase of PEFR by about 3% at 3800 m, similar to Forster's results (at 4200 m). Air density must be considered in future studies in altitude and in estimation of clinical improvement of asthmatic people living in mountain health resort.

Can exhaled nitric oxide differentiate causes of pulmonary fibrosis?

BACKGROUND: Interstitial lung diseases (ILD) comprise a heterogeneous group of disorders, and when diagnosed at the stage of pulmonary fibrosis, the underlying lung disease can sometimes be difficult to identify. The aim of the present study was to determine whether there are differences in FENO (fraction of exhaled nitric oxide) between different subtypes of fibrotic ILD. METHODS: Sixty-one patients, with honeycombing on computed tomography (CT) scan, and whose FENO levels had been measured during chronic dyspnoea evaluation, were divided into four groups based on pulmonary fibrosis aetiology: idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP), connective tissue disease-associated ILD disorders (CTD-ILD), drug-induced pneumonia. The FENO values of each group were compared and CT scan features were analysed to identify the mechanisms involved in FENO change. RESULTS: The median FENO value of patients with chronic HP was 51 ppb (IQR 36-74), higher than that of the other groups (22 ppb (IQR 17-30) in IPF, 19 ppb (IQR 17-21) in drug-induced pneumonia, and 25 ppb (IQR 17-37) for CTD-ILD; p = 0.008). At the cut-off value of 41 ppb, the optimal sensitivity and specificity to diagnose HP with FENO were respectively 76.9% and 85.4%. On CT scans, only extensive lobular areas with decreased attenuation, a recognized marker of bronchiolar disease, were associated with high FENO values (p = 0.0002). CONCLUSION: FENO could be a tool for differentiating chronic HP from other types of pulmonary fibrosis. The mechanism involved seems to be bronchiolar disease.

The radiospirometric flow-volume diagram recording technique and comparative study with conventional spirometry.

The spirometric flow-volume diagram recorded for a forced expiration gives information which is used in assessing obstructive or restrictive pulmonary diseases. Regional data of the same kind can be achieved using a simple radiospirometric technique and scintillation camera. A series of images during inspiration and expiration are defined and a time-activity curve with an integration time constant of about 100-200 ms is obtained from the images during the forced expiration phase. The equivalent of the flow-volume diagram, i.e., the time derivative of the activity vs. activity is computed. There were 21 subjects studied in this series. Normal subjects or patients with various diseases underwent classical spirometry, so that the global radioactive diagram could then be compared to the spirometric flow-volume diagram and its parameters expressed in terms of volumes and flow: vital capacity, peak flow, mean flow, flow at mean volume. The correlation with classical spirometry is highly significant. Similarly regional data are consistent with the pulmonary results.