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.

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.

[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.

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.

Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis.

Using nebulization to deliver aminoglycosides may be of benefit in cystic fibrosis (CF) patients colonized by Pseudomonas aeruginosa. However, one problem with this route is the absence of clinical parameters allowing estimation of the mass of drug deposited in the lungs (MDL). The aim of this study was to assess whether aminoglycoside excretion in the urine reflects the MDL. Fourteen studies were performed in seven CF patients. Amikacin was mixed with albumin labelled with 99mTc and nebulized with an ultrasonic nebulizer. The MDL was determined by the mass-balance technique. Urine was collected during the 24 h following inhalation and was assayed for amikacin by fluorescence polarization immunoassay (FPIA). The mean+/-SEM MDL was 14.0+/-2.2% of the nebulizer charge. The mean+/-SEM amount of amikacin excreted in the urine was 20.9+/-4.5 mg and correlated with the MDL (r=0.93; p=0.0001). There was, however, wide intersubject variability in both deposition and excretion in the urine. Monitoring excretion of aminoglycosides in the urine allows noninvasive estimation of the mass of drug deposited in the lung in cystic fibrosis patients, which might be useful to assess the dose-response relationship in groups of patients, but intersubject variability prevents its use for individual follow-up.

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.

[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.

[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.

[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.

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.

Nebulization and anti-Pseudomonas aeruginosa activity of colistin.

Colistin aerosols are frequently administered to patients with cystic fibrosis. However, questions arise concerning the effect of both jet and ultrasonic nebulizers on the properties of the drug. The aim of this study was to characterize the anti-Pseudomonas aeruginosa (PA) activity of colistin after jet (Pari LL) and ultrasonic (DP100) nebulization. A bench study was performed by capturing the aerosols, determining the drug mass, and assessing its anti-PA activity. Because the inhaled mass of colistin had to be entirely recovered for the bacteriological study, it was assessed by isotopic methods, mixing the drug with a 99mTc-labelled tracer and demonstrating that 99mTc activity accurately predicted the mass of colistin. Colistin was extracted from the filters and its antibiotic activity was determined using the method employed for the study of the bacteriostatic and bactericidal power of serum on the ATCC 27853 PA strain. The postnebulization minimum inhibitory concentrations (MIC) were 1.9 micrograms.mL-1 with DP100 and 0.5 microgram.mL-1 with Pari LL. These values were less than two dilutions different from the 1 microgram.mL-1 MIC of non-nebulized colistin. We conclude that neither jet nebulization nor ultrasonic nebulization alter the antibiotic properties of colistin and that both systems can be used to nebulize colistin.

[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.

Community acquired pneumonia in adults: a study comparing clinical features and outcome in Africa (Republic of Guinea) and Europe (France).

BACKGROUND: Community acquired pneumonia is the most common cause of death from infectious disease both in western and developing countries. A study was carried out in Conakry, Republic of Guinea and Tours, France in order to compare signs, symptoms, severity of illness, risk factors, and clinical outcome of community acquired pneumonia in adult patients admitted to hospital. METHODS: The study was performed in the cities of Conakry and Tours over the same one year period. Patients with nosocomial pneumonia, tuberculosis, and those who were HIV positive were excluded. Data were recorded on the same forms in both centres. A severity score was calculated according to American Thoracic Society criteria. Follow up was evaluated at days 2, 7 and 15. RESULTS: A total of 333 patients (218 from Conakry, 115 from Tours) were included in the study with a diagnosis of community acquired pneumonia, with or without lung abscess or pleural effusion. Mean age was higher and pre-existing illness rate, dehydration, agitation, and stupor were more frequent in patients in Tours. Respiration rates of > 30 breaths/min and the incidence of crackles were identical in the two centres. Fever above 39 degrees C, initial shock, chest pain, and herpes were significantly more frequent in Conakry. Initial chest radiographic abnormalities were similar in the two groups, ranging from unilateral pleuropulmonary involvement (89% and 83% in Conakry and Tours, respectively) to diffuse patchy parenchymal disease. Parapneumonic effusion was present in 17% and 16% of the patients of Conakry and Tours, respectively. Pneumonia was considered to be severe in 33% and 42% of the patients, respectively. In Conakry first line antibiotic therapy was penicillin alone (2 million units a day) for 197 patients (90%) and second line antibiotic therapy was prescribed for 25 patients (12%). In Tours first line therapy consisted of a single antibiotic (amoxicillin, third generation cephalosporins) for 65 patients (57%) and second line antibiotic therapy was prescribed for 55 patients (48%). The clinical outcome was similar in Conakry and Tours: 88% and 85% of patients, respectively, were afebrile or clinically cured at day 15. The mortality rate was similar (6% and 8%, respectively). CONCLUSIONS: The problems encountered in the management of community acquired pneumonia are quite different in western and developing countries. This study shows that low doses of penicillin can cure 90% of African patients with pneumonia as effectively as more aggregative treatments in European patients who are both older and have greater comorbidity. Although pneumococci with reduced penicillin sensitivity occur in western countries, this does not seem to be the case in black Africa. For these reasons, low doses of penicillin or amoxicillin remain good first line treatment.

Predictive value of serum III procollagen for diagnosis of pulmonary involvement in patients with scleroderma.

High resolution computed tomography (HRCT) was recently demonstrated to be as good as open lung biopsy for the diagnosis of pulmonary involvement in patients with scleroderma. Nevertheless, in view of its price and related irradiation, HRCT cannot be recommended as a screening test. Serum III procollagen (sPIIINP) is an aminopropeptide of type III collagen, which is released during conversion into collagen by specific proteases. Increased levels of sPIIINP have been observed in patients with scleroderma. The aim of the present study was to assess the relationship between sPIIINP measurement and pulmonary involvement defined according to HRCT and pulmonary function tests (PFT) with single-breath carbon monoxide transfer capacity (TL,CO) in 28 patients suffering from scleroderma. Patients were divided into two groups for analysis, Group A comprising 16 patients without pulmonary scleroderma and Group B comprising 12 patients with pulmonary scleroderma. All patients had stable cutaneous disease and normal renal and hepatic function. The level of sPIIINP was determined by radioimmunoassay (RIA-gnost P-III-P, Prod. Nr. ODMT; Behring, Marburg, Germany). Mean +/- SD sPIIINP level in Group A was 0.85 +/- 0.21 U.mL-1. Individual values ranged 0.6-1.3 U.mL-1. Mean +/- SD sPIIINP value was 1.30 +/- 0.40 U.mL-1 in Group B and individual values ranged 0.7-1.9 U.mL-1. The difference in mean sPIIINP level between Group A and Group B was significant. Using a cut-off at 1.1 U.mL-1, sensitivity of sPIIINP was 0.66, specificity 0.94, positive predictive value 0.89, negative predictive value 0.79, false positive rate 0.06, and false negative rate 0.33. The value of sPIIINP correlated with HRCT score but not with PFT. This study confirms the relationship between sPIIINP and scleroderma with interstitial lung disease. We suggest that sPIIINP could be measured in patients with scleroderma to screen those patients requiring HRCT. Further studies are necessary to determine the value of sPIIINP in terms of prognosis and follow-up of patients under treatment.

Acute respiratory infections in children: a community-based study comparing a primary health center and a pediatric unit, Republic of Guinea.

OBJECTIVE: A community-based study was carried out in the Republic of Guinea in order to evaluate the frequency of occurrence, severity of illness, risk factors and the results of planned treatment of acute respiratory infections (ARI) in children under the age of 15 years. DESIGN: The study was performed over a 1-year period in 2 distinct areas, 1 rural and 1 urban. A total of 2622 ARI were identified among children under 15 years of age. In the rural area, data were collected by primary health-care workers and by 2 physicians who were trained to supervise the study. RESULTS: Among the rural population, 1422 ARI were identified. In the city center, Conakry, 1200 ARI were identified in one children's hospital. The child population under 5 years of age was significantly greater in the rural area (95.2%) than in the city center (83.2%) (P < 0.0001). Malnutrition affected 10.6% of all the children. There were discrepancies in symptoms and signs affecting the 2 groups but the severity scores, including children under 5 years of age, were not significantly different: including children under 5 years of age, were not significantly different: 10-11% of the children were considered to have severe disease and 6.2% required urgent referral to hospital. Upper and lower respiratory infections (URI and LRI) were equally represented (49.9% and 50.1% respectively). Distribution of each type of ARI was significantly different in the 2 groups: there were significantly more URI in the city center, especially tonsillitis. Bronchitis and bronchopneumonia occurred significantly more often in the rural area. Pneumonia and bronchopneumonia represented 9.8% of all ARI. Use of antibiotic therapy was known in 2557 patients: 1268 URI and 1289 LRI. In children with URI, 69.7% did not receive antibiotic therapy, 29.9% received 1 antibiotic and 0.03% received 2 antibiotics successively. Children from the city center received significantly more antibiotics than in the rural health center. In children with LRI, 17.8% did not receive antibiotic therapy, 81.7% received 1 antibiotic and 0.05% received 2 antibiotics successively. There was no significant difference between the 2 centers in antibiotic prescription. Clinical outcome showed that 93% of children were considered to be cured at day 7 and 99.4% at day 14. 14 children with severe pneumonia died. The infection cost (antibiotics plus other drugs prescribed as supportive care) was 0.45 US$ per child in the rural area and 9.7 US$ in the children's hospital. CONCLUSION: This supervised study constitutes the first large longitudinal study concerning respiratory infections in West Africa. It demonstrates that simple guidelines are valid in order to prevent mortality and complications. Care appropriate to population requirements in term of infectious diseases can be delivered with low cost and low technology.

[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.

[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)

Direct isotopic assessment of aerosolized pentamidine deposition: influence of nebuliser.

OBJECTIVES: The aim of the present study was to compare the efficiency of pulmonary deposition of pentamidine using the Respirgard II jet nebuliser or the Fison ultrasonic nebuliser with 99m technetium (99m Tc) labelled pentamidine in the current conditions of recommended treatment. The study was designed in three stages, to verify particle size distribution, to validate the isotope labelling, and to compare pulmonary deposition of pentamidine isethionate with the two nebulisers. METHODS: Count median aerodynamic diameter and mass median aerodynamic diameter were measured using the velocimetry technique and aerosol dispersion was calculated according to the standard deviation defined by the ratio of diameters between 84.3% and 50% of the total distribution. Stability of labelling was checked both in vitro, by radiochromatography, and in vivo, by the absence of free technetium thyroid fixation after intravenous injection of the preparation to a rat and inhalation by baboons. The direct isotopic technique was used to compare pulmonary deposition of 300 mg aerosolized 99m Tc labelled pentamidine isothionate with the two nebulisers in four HIV patients treated with primary prophylaxis. RESULTS: Count median aerodynamic diameter and mass median aerodynamic diameter (MMAD) were higher with Fisoneb than with Respirgard II. Nevertheless Fisoneb MMAD remained in the optimal range for peripheral deposition. In one patient, pentamidine lung burden was higher using the Respirgard II (13% of dose originally in nebuliser) when compared with the Fisoneb (10.2% of dose originally in nebuliser). A better result was obtained in the 3 other patients with Fisoneb (mean = 14.3%) compared with Respirgard II (mean = 3.8%). In all 4 patients gastric contamination was higher with Fisoneb (mean = 5.2%) as compared with Respirgard II (mean = 2.6%). Cough and bronchospasm were not observed with either device. CONCLUSION: This study showed that Fisoneb, a practical and cheap nebuliser which has proved to be effective in clinical studies when used for pentamidine nebulisation, leads to correct particle size distribution and pulmonary deposition of the drug. We believe that such studies to evaluate aerosol characteristics should be recommended for any kind of nebuliser.

[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.