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The Mastersizer X (Malvern Instruments) used to be the reference device for assessing droplet size distribution of aerosols by laser diffraction, but it has not been updated and has gradually been replaced by the Spraytec (Malvern Instruments), which is considered to provide greater accuracy and higher acquisition speed.The aim of this study was to compare the use of the two diffractometers to characterize medical liquid aerosols in a wide range of droplet sizes, using four nasal sprays to produce large droplets (10-180 μm) and 10 nebulizers to produce smaller droplets (0.5-20 μm). The influence of the inhalation cell provided with the Spraytec on the measurements was also determined.Correlation between the devices was low for large droplets (R(2)=0.37) and high for smaller droplets (R(2)=0.97). The Spraytec overestimated the median diameter of small droplets by 14%, and Bland-Altman tests showed no equivalence (limits of agreement over 20%). An artifact peak in the large size range was observed with the Spraytec, which could be due to difficulty for the multiple scattering algorithm to process high-density aerosol clouds. The difference was reduced to 5% by using the inhalation cell provided by the Spraytec with a 15 L/min aspiration.The Mastersizer X and the Spraytec cannot be considered as equivalent laser diffraction devices, but the difference can be reduced with the Spraytec inhalation cell.

Summary 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 FE NO (fraction of exhaled nitric oxide) between different subtypes of fibrotic ILD. Methods Sixty-one patients, with honeycombing on computed tomography (CT) scan, and whose FE NO 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 FE NO values of each group were compared and CT scan features were analysed to identify the mechanisms involved in FE NO change. Results The median FE NO 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 FE NO 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 FE NO values ( p = 0.0002). Conclusion FE NO could be a tool for differentiating chronic HP from other types of pulmonary fibrosis. The mechanism involved seems to be bronchiolar disease.

The purpose of this study was to determine the ability of technetium-99m J001X scintigraphy to image active pulmonary involvement in patients suffering from rheumatoid arthritis (RA). J001X is a fully characterized acylated poly(1,3)galactoside, isolated from Klebsiella membranes, which is able to bind recruited macrophages after aerosol administration. J001X scintigraphy was compared with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs) and bronchoalveolar lavage (BAL) in 15 patients suffering from RA. Patients were considered to have pulmonary involvement when they had an interstitial syndrome on HRCT and a decrease of 20% in TCO/VE (transfer coefficient) on PFTs and/or an abnormal BAL (lymphocytosis higher than 20% and/or percentage of neutrophils higher than 10%). Pulmonary involvement was present in eight patients, and absent in seven. Of the eight patients with pulmonary involvement, all had abnormal BAL, two had an interstitial syndrome on HRCT, two had decreased TCO/VE and three had positive J001X scintigraphy. Of the seven patients without pulmonary involvement, six had normal BAL (not available in one), two had an interstitial syndrome on HRCT, one had decreased TCO/VE and two had positive J001X scintigraphy. According to our gold standard of pulmonary involvement, the sensitivity of J001X scintigraphy for the detection of pulmonary involvement in RA was 37.5%, the specificity was 71.4% and the positive predictive value was 60%. The ability of J001X scintigraphy to detect active pulmonary involvement during RA appears unclear in this study but it may detect processes unnoticed by the other modalities. These patients will be followed 12 and 24 months later and the changes in J001X scintigraphy, HRCT and PFTs will be compared to demonstrate whether J001X scintigraphy is able to assess an active process in the pulmonary involvement during RA and to specify its predictive value.

The aim of the present study was to characterize amphotericin B aerosols nebulized by ultrasonic and jet nebulizers and to study their deposition and pharmacokinetics in patients with pulmonary mycetoma. The aerodynamic behaviour and pulmonary deposition of amphotericin B particles were measured using a direct isotopic method based on stable labelling of the drug with 99mTc. Each nebulizer was bench tested for inhaled mass and particle size distribution. Three patients suffering from pulmonary aspergilloma were enrolled for a 4 week clinical study. They received 5 mg of amphotericin B daily delivered by either Fisoneb or DP100 (ultrasonic) or Respirgard II (jet) nebulizers. Deposition of radiolabelled amphotericin B was measured once with each nebulizer using a gamma-camera. In two patients, amphotericin B serum concentration was monitored over a 330 min period after the nebulization had been completed. Inhaled masses of the three nebulizers, assessed as % of labelled drug caught in inspiratory filter in duplicate experiments, were: 5.8 and 3.6% for Respirgard II; 26.5 and 28.3% with Fisoneb; 5.9 and 6.3% for DP100. Mass median aerodynamic diameter (mean +/- SD) results were: 0.28 +/- 0.04 micron with Respirgard II; 4.82 +/- 0.78 microns with Fisoneb; and 2.27 +/- 1.14 microns with DP100. Because of larger particles and significantly greater inhaled mass, Fisoneb delivered more amphotericin B to the central airways, the lung periphery and in the mycetoma lung regions. Amphotericin B serum concentrations correlated with pulmonary deposition and remained below 25 ng.mL-1. No untoward effects were reported by the patients during the 4 week trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Introduction Historiquement decrite comme une fibrose des sommets pulmonaires, la fibro-elastose pleuroparenchymateuse (FEPP) est une entite du groupe des pneumopathies interstitielles idiopathiques rares depuis 2013. Le diagnostic est suspecte devant l’imagerie guidee par la clinique, la confirmation est histologique sans presager de l’etiologie. Observation Un homme âge de 72 ans presentait une dyspnee chronique croissante avec une toux seche matinale et des crepitants secs aux apex. Son tabagisme etait a 5 paquets-annee sevre. Ses trois freres etaient decedes de fibrose pulmonaire. Le scanner montrait des images de pneumopathie interstitielle commune atypique des deux lobes superieurs. L’endoscopie bronchique et le lavage broncho-alveolaire etaient normaux. Le bilan auto-immun trouvait un facteur antinucleaire a 1/400 sans specificite. Face a l’absence de diagnostic et l’aggravation du syndrome restrictif aux explorations fonctionnelles respiratoires, une biopsie chirurgicale etait realisee, retrouvant des lesions fibro-elastosiques focales en sous pleural, le long des septa interlobulaires et une transition nette avec le parenchyme pulmonaire sain sous-jacent. Conclusion La recherche de symptomes respiratoires chez les apparentees de patients atteints d’une pneumopathie interstitielle diffuse pourrait etre utile pour le depistage des formes familiales. L’unique traitement efficace, demeure a ce jour, la transplantation pulmonaire.

Introduction La question du depistage precoce du cancer broncho-pulmonaire (CBP) constitue un enjeu de sante publique. Pour certains, l’emphyseme pulmonaire chez les patients BPCO pourrait etre un facteur de risque de la survenue de ces CBP. Notre objectif etait d’evaluer l’association entre emphyseme pulmonaire et CBP dans une population BPCO. Methodes Nous avons compare dans une etude retrospective cas-temoins dans le service de pneumologie du CHRU de Tours, 76 patients presentant un CBP et BPCO diagnostiques entre janvier 2013 et janvier 2014, avec 76 patients BPCO temoins sans CBP apparies sur l’âge, le sexe, le tabagisme (± 10 PA) et la gravite de la BPCO (stade GOLD). Chaque patient inclus devait avoir beneficie d’un scanner thoracique. L’emphyseme etait calcule de maniere automatisee par un logiciel de post-traitement en considerant un seuil de −950 unites Hounsfield (UI) et compare entre les deux groupes. Les caracteristiques cliniques (IMC, comorbidites, nombres d’exacerbation), biologiques (albumine, CRP), fonctionnelles (VEMS) et les traitements (de la BPCO et statines) etaient aussi compares entre les 2 groupes. Resultats Le taux d’emphyseme etait diminue de maniere significative dans le groupe BPCO-CBP par rapport au groupe BPCO seule : 6,88 % versus 12,41 % (p = 0,02). Cette difference n’etait pas retrouvee lorsque l’histologie du CBP etait un adenocarcinome. Par contre, elle etait retrouvee chez les BPCO-epidermoides par rapport a leurs apparies : 1,8 % versus 5,6 % (p = 0,01). Il existait une difference significative de prise en charge medicamenteuse de la BPCO entre les groupes, seulement 18 % des patients CPB + BPCO beneficiant d’un traitement contre 74 % dans le groupe BPCO seule (p = 0,001). Conclusion Dans notre etude, l’emphyseme pulmonaire ne semble pas etre un facteur favorisant l’apparition d’un CBP. La presence d’un emphyseme ne serait donc pas une caracteristique conduisant a la realisation d’un depistage du CBP chez un fumeur.

ATS 2012 Study Of The Effectiveness Of A New Inhalation Chamber In Invasive Mechanical Ventilation N. Boukhettala, P. Diot, L. Vecellio Laboratoire ProtecSom Valognes/FR, INSERM U618 Tours/FR, Aerodrug Tours/FR Laboratoire INSERM U618 Rationale: The aim of this study was to evaluate the effectiveness of a new inhalation chamber (PX01) connected with a pMDI and a nebulizer in invasive mechanical ventilation. Methods: To assess the PX01 inhalation chamber in clinical conditions, assembly below including a respirator (Volume controlled, Vc = 450mL, f = 15/min, PEEP = 6, P max = 19, Ti / Ttot = 40/60) and a model of adult lung Dual TTL model 5600i (Michigan Instruments) was used. A filter was placed after the endotracheal tube to measure salbutamol by spectrophotometry after nebulization and after aerosolization. Results: After nebulization, the mass of salbutamol deposited on the filter, that is located after the endotracheal tube, was twice higher with the PX01 inhalation chamber than the Aerogen T-adapter (659.7±224.6 μg vs 312.9±100.2 μg). In addition, the PX01 inhalation with a short cone was more effective than the PX02 inhalation chamber with a long cone (659.7±224.6 μg vs 477.7±167.5 μg). After aerosolization, the mass of salbutamol deposited on the filter was similar between the Ace Spacer and the PX01 inhalation chamber (181.1±54.4 μg vs 225.4±60.1 μg). Conclusion: In conclusion, the PX01 inhalation chamber increased the efficacy of nebulization in invasive mechanical ventilation.

Ulcerative colitis (UC) is an inflammatory bowel disease that can on rare occasions affect the respiratory tract. We report the case of a 32-year-old woman suffering from UC, for whom 2-deoxy-2[(18)F]fluoro-D-glucose positron emission tomography ((18)F-FDG PET) was useful, both for diagnosis and management of tracheal involvement. She presented with severe cough and fever, and bronchoscopy revealed inflammation of the trachea. Infection, vasculitis and relapsing chondritis were first ruled out. Lymphoma was then suspected, and (18)F-FDG PET was performed, but revealed only a moderately increased uptake on the posterior wall of the trachea. Histological findings revealed non-specific inflammation. Systemic corticosteroids were prescribed and symptoms improved rapidly. After 3 months, bronchoscopy showed a significant reduction of the local inflammation, and (18)F-FDG PET did not reveal the previous abnormal tracheal (18)F-FDG uptake. Management of tracheal involvement of UC requires close monitoring. However, repeated bronchoscopies can be harmful in these inflammatory situations, and non-invasive techniques could be useful. (18)F-FDG PET is used for the follow-up of digestive involvement of UC, but extra-intestinal locations have not been evaluated. Our case highlights the potential interest of (18)F-FDG PET for tracheal involvement of UC, allowing a non-invasive assessment of local inflammation.

National audience; Objectifs : L'administration nasale de médicaments sous forme d'aérosol est largement utilisée par les otorhinolaryngologistes. Bien qu'elle manque d'évaluations cliniques, la nébulisation ORL se présente comme une option thérapeutique intéressante pour l'administration nasale de médicaments. Les aérosols permettraient de cibler les sites anatomiques d'intérêt situés derrière la valve nasale. Le nébuliseur sonique NL11SN utilise l'addition d'un son de 100 Hertz (Hz) à l'aérosol produit afin d'améliorer le dépôt dans les sinus. L'objectif de notre étude était : (1) d'évaluer in vivo chez le volontaire sain l'influence du son sur la ventilation sinusienne et le dépôt nasal et pulmonaire d'un aérosol sonique, et (2) de quantifier in vitro le dépôt d'aérosols soniques dans les sinus maxillaires d'un modèle plastiné. Patients et méthodes : In vivo, une scintigraphie de ventilation au gaz 81mKr et une scintigraphie de dépôt d'aérosol (99mTc-DTPA) sonique produit par le NL11SN étaient réalisées chez sept volontaires sains. En parallèle, des nébulisations de gentamicine étaient réalisées en présence ou en absence du son de 100 Hz sur un modèle de tête humaine plastinée avec le NL11SN. La quantité de gentamicine déposée dans les sinus était dosée par FPIA. Résultats : L'addition du son de 100 Hz au gaz 81mKr permettait la ventilation des cavités sinusiennes des volontaires sains. Le 99mTc-DTPA nébulisé avec le NL11SN chez les volontaires se déposait majoritairement dans les cavités nasales (2/3 vs 1/3 dans les poumons). In vitro, le NL11SN utilisé en mode sonique a permis d'augmenter d'un facteur 3 (p < 0,002) le dépôt de gentamicine dans les sinus du modèle plastiné. Les quantités d'antibiotiques déposées dans les sinus du modèle plastiné pouvaient être considérées comme suffisantes pour avoir un effet thérapeutique local. Conclusions : Le nébuliseur NL11SN assure un dépôt préférentiel de l'aérosol dans les cavités nasales et cible efficacement les sinus maxillaires.

International audience; Aim: Intranasal aerosol administration of drugs is widely used by ENT specialists. Although clinical evidence is still lacking, intranasal nebulization appears to be an interesting therapeutic option for local drug delivery, targeting anatomic sites beyond the nasal valve. The sonic nebulizer NL11SN associates a 100 Hertz (Hz) sound to the aerosolization to improve deposition in the nasal/paranasal sinuses. The aim of the present study was: to evaluate in vivo the influence of associating a 100 Hz sound on sinus ventilation and nasal and pulmonary aerosol deposition in normal volunteers, and; to quantify in vitro aerosol deposition in the maxillary sinuses in a plastinated head model. Material and methods: Scintigraphic analysis of 81mKr gas ventilation and of sonic aerosol (99mTc-DTPA) deposition using the NL11SN was performed in vivo in seven healthy volunteers. In parallel, NL11SN gentamicin nebulization was performed, with or without associated 100 Hz sound, in a plastinated human head model; the gross amount of gentamicin delivered to the paranasal sinuses was determined by fluorescence polarization immunoassay. Results: Associating the 100 Hz sound to 81mKr gas ensured paranasal sinus ventilation in healthy volunteers. 99mTc-DTPA particles nebulized with the NL11SN were deposited predominantly in the nasal cavities (2/3, vs 1/3 in the lungs). In vitro, the use of NL11SN in sonic mode increased gentamicin deposition threefold in the plastinated model sinuses (P < 0.002); the resulting antibiotic deposit would be sufficient to induce a local therapeutic effect. Conclusion: The NL11SN nebulizer ensured preferential nasal cavity aerosol deposition and successfully targeted the maxillary sinuses.

BACKGROUND--J001X is an acylated poly-galactoside isolated from the membrane of Klebsiella and able to interact with macrophages, mainly in their activated state. The aim of the present study was to determine the ability of 99m-labelled technetium (99mTc)-J001X scintigraphy to image pulmonary disease, defined by high resolution computed tomographic scanning and pulmonary function tests, in patients suffering from scleroderma. METHODS--Patients were considered to have pulmonary disease when they had at least two positive signs on high resolution computed tomography, or a decrease in lung volume and single breath carbon monoxide transfer, or both, with no disease process other than scleroderma in their medical history. Positive J001X scintigraphic imaging was defined by symmetrical bilateral pulmonary fixation three and five hours after inhalation of 99mTc-J001X. J001X scintigraphic results were compared with disease activity as indicated by bronchoalveolar lavage (BAL) fluid lymphocytosis. RESULTS--Seventeen patients were studied, in 12 of whom J001X scintigraphy was positive. There was no correlation between BAL lymphocytosis and J001X scintigraphic findings, nor between BAL and pulmonary scleroderma. This was not surprising because of the high specificity of macrophage targeting by J001X. CONCLUSIONS--Follow up of a larger population over a longer period is needed to establish whether there is a prognostic value for positive J001X scintigraphic findings in scleroderma.

Discrepancies have been reported in differential cell counts according to the diverse processing methods used in bronchoalveolar lavage (BAL) fluid management. The differences have proved to be mainly the result of selective lymphocyte loss, while the exact mechanisms of the phenomenon remain controversial. Observing a similar variation in differentials from differently stained identical smears, we quantified the cell loss due to staining procedures from 45 consecutive satisfactory BAL procedures. To do this, we compared relative lymphocyte recovery on neat pooled lavage in a hemocytometer with that from smears and cytopreps fixed and stained in different ways. We found (1) A significant lymphocyte loss (p < 0.05) whatever the staining method. (2) Different methods of fixation and staining lead to considerable variation in differentials from slides otherwise identically managed. The loss is higher during air-drying fixation followed by staining with an aqueous medium such as Diff-Quik than on spray-fixed slides stained in an alcohol medium such as Papanicolaou stain. (3) The effect of lymphocyte loss on differentials is more important when the initial lymphocytosis is less than 35%, and decreases to nonsignificance when it exceeds 70%. The role of cytocentrifugation or other manipulations in cell loss probably has been overestimated because unknown effects of staining methods were also attributed to these manipulations. We suggest that lymphocyte loss could arise from poor adherence on slides, which is exacerbated during aqueous staining if no artifice (e.g., spray fixation), is used to hold them. Thus, the definition of the long-awaited standard procedure for an accurate differential count of BAL fluid must take into account fixation and staining methods.

The inhaled route is increasingly developed to deliver locally acting or systemic therapies, and rodent models are used to assess tolerance before clinical studies. Endotracheal intubation of rats with a probe which generates powder aerosols enables controlled administration of drug directly into the respiratory tract. However, preliminary observations of intratracheal powder administration procedures have raised concerns with regard to pulmonary safety. The aim of the present work was to evaluate the safety of intra-tracheal administration of dry powder in a rat model. Sixty animals were administered various volumes of air alone, lactose or magnesium stearate through a Microsprayer® (Pencentury, USA). The mass of powder actually delivered to each animal was calculated. Rats were sacrificed immediately after administration, and the lungs, trachea and larynx were removed and examined for gross pathology. The mass of powder delivered varied, the full dose being rarely delivered. About one third of the administration procedures resulted in respiratory failure, and macroscopic pulmonary lesions were observed in about 55% of animals. Lung damages were observed with air alone, lactose and magnesium stearate. In conclusion, artifacts observed with this technique may limit the relevance of the model. These observations are particularly important in the context of regulatory toxicity studies.

We report five cases of asthma unmasked by anti-tumor necrosis factor (TNF)-α-blocking drugs. Asthma symptoms appeared within an average of 4 months (range 1-24 months) after starting the anti-TNF-α treatment for inflammatory disease. The patients did not appear to be predisposed to asthma except for one patient who had asthma during childhood. Four patients stopped anti-TNF-α-blocking drugs with an improvement of symptoms within 1 to 5 months. In the patient with a history of childhood asthma, respiratory symptoms recurred when another anti-TNF-α therapy was started. Asthma control was achieved with inhaled steroids, allowing anti-TNF-α treatment to continue. The biotherapy was maintained for the fifth patient in association with inhaled steroids. The pathophysiologic mechanisms are unknown but are probably more complex than the T helper 1/T helper 2 imbalance suggested in the literature, and further studies are required.

Lung cancer is the leading cause of cancer-related death worldwide. The efficacy of current systemic treatments is limited, with major side effects and only modest survival improvements. Aerosols routinely used to deliver drugs into the lung for treating infectious and inflammatory lung diseases have never been used to deliver monoclonal antibodies to treat lung cancer. We have shown that cetuximab, a chimeric anticancer anti-EGFR mAb, is suitable for airway delivery as it resists the physical constraints of aerosolization, and have evaluated the aerosol delivery of cetuximab in vivo.We developed an animal model of lung tumor sensitive to cetuximab by injecting Balb/c Nude mice intratracheally with A431 cells plus 10 mM EDTA and analyzed the distribution, pharmacokinetics and antitumor efficacy of cetuximab aerosolized into the respiratory tract.Aerosolized IgG accumulated durably in the lungs and the tumor, but passed poorly and slowly into the systemic circulation. Aerosolized cetuximab also limited the growth of the mouse tumor. Thus, administering anticancer mAbs via the airways is effective and may limit systemic side effects.Delivery of aerosolized-mAbs via the airways deserves further evaluation for treating lung cancers.

International audience

International audience

Shrinking lung syndrome is a rare complication of systemic autoimmune diseases, mainly systemic lupus erythematosus, but also Sjogren's syndrome and polymyositis. It should be suspected in any patient with autoimmune disease presenting with an unexplained dyspnea. Shrinking lung syndrome is characterized by small lung volumes, elevation of the diaphragm and restrictive physiology without parenchymal involvement. Its pathogenesis remains controversial: diaphragm dysfunction, phrenic neuropathy or pleural inflammation. Pleural adhesions and pain probably play a significant role in the pathogenesis. Electrical or magnetic phrenic stimulation is an important method of investigation but it is not widely available. No treatment has been validated. Steroids are proposed as first-line treatment, alone or associated with β2-adrenergic receptor agonists. In refractory cases, immunosuppressors are used. Biotherapies may be beneficial. Long-term prognosis is good, but respiratory failure can occur in some cases.

A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of aerosol delivery device that is most suitable for their patient. The focus of the consensus statement is the patient-use aspect of the aerosol delivery devices that are currently available. The subject was divided into different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. To achieve consensus, draft reports and recommendations were reviewed and voted on by the entire panel. Specific recommendations for use of the devices can be found throughout the statement. Healthcare providers should ensure that their patients can and will use these devices correctly. This requires that the clinician: is aware of the devices that are currently available to deliver the prescribed drugs; knows the various techniques that are appropriate for each device; is able to evaluate the patient's inhalation technique to be sure they are using the devices properly; and ensures that the inhalation method is appropriate for each patient.

Aerosol therapy is an expanding technique allowing administration of drugs acting locally in the bronchial tree and lungs or acting systemically after absorption through the respiratory tract. However, the choice of solvents and adjuvants is a critical step in the formulation process of new drugs. Pulmonary tolerance of ethanol, propylene glycol and sorbitan ester was evaluated in a rat model of intratracheal administration using a Microsprayer in a 4-day toxicity study.Four groups of Sprague-Dawley rats (11 rats per group, n = 44) have received, on 4 consecutive days 150 microL of solutions containing the solvents, by intratracheal route using a IA-1B-2 inches-Microsprayer (PennCentury, Philadelphia, PA). Once a day, the rats received deionized water (control) or ethanol 10% or propylene glycol 30% or sorbitan monooleate 10%. All rats were sacrificed 24 h after the fourth administration. Biochemical analysis on bronchoalveolar lavage (BAL) fluid was performed on seven rats per group. The respiratory tract of the remaining four rats/group was examined histologically.Biochemistry and histopathology findings demonstrated that under the conditions tested, deionized water, 10% ethanol, and 30% propylene glycol were tolerated in a qualitatively similar way presenting limited cellular reaction. In contrast, 10% sorbitan monooleate produced an accumulation of foamy macrophages in the lungs and a higher degree of inflammation. In addition, animals in this group showed higher polymorphonuclear neutrophil recruitment and total proteins levels in BAL fluid.The overall results recommended ranking the vehicles according to the degree of inflammation which was induced: deionized water10% ethanolor =30% propylene glycol10% Tween 80.

A glycolipid (J001X) isolated from the membrane proteoglycans of a non-pathogenic strain of Klebsiella pneumoniae was developed to bind selectively to macrophages. A scintigraphic technique could thus be developed and applied to an experimental model of lung berylliosis. Six baboons were injected intratracheally with a beryllium metal suspension. Three to 24 months later, they were submitted to both an anatomical and a functional respiratory evaluation. Two baboons were explored at the early stage of alveolitis and four baboons at a more advanced stage characterised by a granulomatous disorder. Scintigraphy was performed using J001X labelled with 99mtechnetium administered as an aerosol. In the six baboons, conventional imaging techniques (chest x ray film, computed tomography scan, gallium scintigraphy), failed to show either any lung abnormality or mediastinal lymph nodes consistent with beryllium disease. In the two recently contaminated baboons, J001X scintigraphy showed a well defined parenchymal fixation facing the contaminated lobe. In the four baboons who were at a more advanced stage of berylliosis, J001X fixation was always focused paratracheally without any significant involvement of the lung parenchyma. The subcarinal and laterotracheal lymph nodes seen at necropsy corresponded to J001X scintigraphic fixations. In conclusion, when compared with conventional techniques such as chest x ray film, computed tomography scan, magnetic resonance imaging, and gallium scintigraphy, J001X scintigraphy has proved its ability to detect occult lesions in experimental berylliosis in baboons. By comparison with gallium scintigraphy, scintigraphy with J001X appears to have superior sensitivity and can be performed in four hours.

International audience

Purpose. To explore the feasability of imaging lung masses with a novel endobronchial linear-array transducer. Method. We used a linear-array transducer of 7 F (2.3 mm in diameter) operating at a center frequency of 10 MHz for endobronchial imaging. We used the probe in 20 subjects with suspected lung cancer to identify and measure the tumor; to asses the tumor's sonographic characteristics, bronchial wall invasion, and presence of lymph nodes; to guide a transbronchial needle aspiration (TBNA); and to evaluate potential side effects. Results. In all patients, the tumor was identified and the relationship with the bronchial wall correctly evaluated through the depiction of a 3-layer wall pattern. Bronchial wall invasion was suspected in 5 patients, small adjacent lymph nodes were detected in 3 patients, and a small pleural effusion was observed close to the lung lesion in 2 patients. The linear-array probe allowed the guidance of successful TBNA with no complications. Conclusion. This feasibility study shows that the prototype probe can be used to depict pulmonary lesions and to guide biopsy nodes. Larger series are needed to validate its usefulness in clinical work-ups and patients management. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008

Primary leiomyosarcoma of the pulmonary artery is an extremely rare tumor that is frequently misdiagnosed as chronic pulmonary embolism. In the present case, early diagnosis and location in the left pulmonary artery permitted resection by pneumonectomy with total cardiopulmonary bypass.

Introduction L’oxygenotherapie nasale a haut debit humidifie (ONHD) est une technique d’utilisation croissante. Les patients de reanimation, susceptibles d’en beneficier, necessitent souvent des bronchodilatateurs inhales. Sur un modele pediatrique (banc in vitro), la masse d’aerosol emise (ME) a l’extremite des canules d’ONHD variait de 2 a 11 % [1] . Chez l’adulte la ME est inconnue, de meme que la masse respirable (MR) susceptible d’etre delivree au niveau du site d’action pulmonaire. L’objectif de cette etude etait d’etudier sur banc adulte les facteurs susceptibles d’influencer ce rendement de la nebulisation au cours de l’ONHD. Materiel et methodes La ME a ete mesuree apres nebulisation de salbutamol (10 mg/5 mL) (Aeroneb ® place avant la chambre d’humidification) a trois debits d’ONHD (30, 45 et 60 L/min). Pour chaque debit d’OHND, la MR a ete mesuree en aval d’un modele anatomique reproduisant le depot ORL et selon deux profils respiratoires simules (respiration calme et en detresse avec des debits inspiratoire moyens respectifs de 15 et 45 L/min). Les pertes environnementales d’aerosol ont ete estimees en se fondant sur la conservation de masse (pertes = ME - MR - depot ORL). Chaque condition a ete repetee six fois. Resultats La ME etait de 22 a 37 % de la masse chargee dans le nebuliseur et variait inversement aux debits d’ONHD. La MR etait de 2 a 13 % de la masse chargee selon les conditions. Elle etait significativement superieure lors de la simulation d’une detresse respiratoire par comparaison a la respiration calme pour chaque debit d’OHD. Cette MR superieure etait associee a un depot ORL inchange et donc en rapport avec une diminution significatives des pertes environnementales d’aerosol ( Fig. 1 ). Discussion Positionne en amont de la chambre d’humidification, un nebuliseur a tamis vibrant semble delivrer une quantite de salbutamol susceptible de produire l’effet clinique recherche. L’augmentation des debits d’OHND serait associee a une moindre masse de salbutamol delivree. A l’inverse, l’augmentation du debit inspiratoire du patient, simulant une detresse respiratoire, serait associee a une augmentation de la masse respirable parvenant au site d’action pulmonaire. La nebulisation a des debits eleves et superieurs au debit inspiratoire du patient, jamais evaluee auparavant, serait a l’origine de fuites durant la phase inspiratoire. Ces fuites inspiratoires diminueraient quand le debit inspiratoire du patient augmente et deviendrait plus proche du debit delivre. Cette etude pose les fondements pour l’evaluation clinique de la nebulisation au cours de l’ONHD.

Introduction Le role exact des IgG4, sous classe d’immunoglobuline G, n’est pas bien connu. Peu de donnees sont disponibles sur la presence des IgG4 aux cours des pathologies pulmonaires. Un asthme serait present chez 20 % des patients atteints par un syndrome d’hyper-IgG4. Notre hypothese est qu’une elevation des IgG4 pourrait etre associee a un phenotype particulier d’asthme. Methodes Dans une etude retrospective menee de janvier 2006 a juillet 2014, un dosage a ete realise dans le cadre du bilan d’asthme difficile chez 122 patients. Les donnees de patients asthmatiques avec une elevation des IgG4 (definie par un rapport IgG4/IgG superieur a 10 %) ont ete comparees a celles des patients asthmatiques sans elevation des IgG4. Resultats Une elevation des IgG4 etait retrouvee chez 17 % des patients avec un asthme difficile. Les patients avec des IgG4 augmentees avaient une FeNO mediane significativement plus elevee (62 [41–115] ppb vs 36 [24–51] ppb). L’eosinophilie sanguine mediane etaient egalement significativement plus elevee (0,21 [0,08–0,53] G/L vs 0,86 [0,56–1,69] G/L). Dans le groupe avec IgG4 augmentees, on trouve une tendance non significative a un moins bon controle de l’asthme (68 % de non controle vs 51 %). Aucun patient ne presentait d’argument pour un syndrome d’hyper-IgG4. Discussion et conclusion Nous observons dans notre cohorte d’asthme difficile qu’une elevation des IgG4 est frequente et possiblement associee a une hypereosinophilie. On suppose que l’activation de certain lymphocyte T regulateur ou B regulateur vont favoriser la secretion d’IgG4 (sous l’action de l’IL-10) en reponse a l’activation des lymphocytes TH2, refletee par l’elevation des eosinophiles.

Le role exact des IgG4, sous-classe d’immunoglobuline G, n’est pas bien connu. Peu de donnees sont disponibles dans les pathologies pulmonaires. Dans une etude retrospective, le lien entre l’augmentation des IgG4 seriques et l’asthme a ete analyse. Parmi 694 patients ayant beneficie d’un dosage des sous-classes d’IgG dans le service de pneumologie du CHRU de Tours de janvier 2006 a juin 2013, 52 presentaient un taux d’IgG4/IgG > 10 %, seuil defini comme pathologique dans la litterature et parmi eux 11 avaient un diagnostic d’asthme selon la definition du GINA. Parmi ces patients, on identifiait 2 asthmes atopiques en cours de desensibilisation dont on sait qu’elle augmente les IgG4. Il existait egalement 3 aspergilloses bronchopulmonaires allergiques, 1 asthme avec obesite, 1 granulomatose eosinophilique avec polyangeite. Quatre patients ne repondaient a aucun phenotype. Ils s’agissaient de 2 hommes et 2 femmes âges de 42 a 77 ans avec une hypereosinophilie moderee associee a des IgE totales basses et aucune sensibilisation aux prick-tests. Le bilan auto-immun etait negatif. L’augmentation des IgG4 seriques dans l’asthme est un evenement rare qui ne repond pas a un seul phenotype. Cependant certains patients presentent un asthme avec hypereosinophilie moderee sans etiologie evidente. Aucun prelevement histologique n’etait disponible mais pourrait s’averer utile a la recherche d’une etiologie.

L’hyperplasie neuroendocrine pulmonaire diffuse idiopathique (DIPNECH) est une maladie rare liee a une infiltration des voies aeriennes par des cellules neuroendocrines favorisant une obstruction bronchique. Aucun traitement n’a prouve une efficacite pour limiter l’evolution de la DIPNECH. Nous presentons le cas d’une patiente âgee de 61 ans, atteinte de DIPNECH revelee par une dyspnee d’effort progressive sur 4 ans et compliquee un trouble ventilatoire obstructif evolutif et severe (VEMS = 700 mL soit 39 % en 2010 et VEMS = 440 mL soit 25 % de la valeur predite en 2014). Le scanner thoracique montrait un poumon en mosaique en rapport avec une bronchiolite diffuse et de multiples tumeurs carcinoides. Le diagnostic etait confirme par biopsie pulmonaire chirurgicale. Alors que la patiente etait recusee pour la transplantation pulmonaire, un traitement par inhibiteur de mTor, le sirolimus a la dose de 2 mg/j lui a ete proposee. Apres 6 mois de traitement par sirolimus, la patiente presentait une amelioration de la dyspnee (passant d’un stade III a un stade II MMRC), une diminution de la neuron specific enolase (NSE) (7 ng/mL sous traitement versus 19 ng/mL avant traitement). Les EFR montraient une relative amelioration du trouble ventilatoire obstructif (VEMS = 550 mL soit 32 % de la valeur predite). Le scanner thoracique montre une stabilite des tumeurs carcinoides et une amelioration des zones d’attenuation lobulaire liee a la DIPNECH. La tolerance du sirolimus etait bonne en dehors de l’apparition d’un diabete non-insulino-dependant. En conclusion, les inhibiteurs de mTor pourraient avoir un effet benefique pour limiter l’evolution des DIPNECH.

EPI-hNE4 (depelstat) is a potent inhibitor of human neutrophil elastase derived from human inter-alpha-trypsin inhibitor and designed to control the excess proteolytic activity in the sputum of cystic fibrosis patients. We analyzed its resistance to the proteolysis it is likely to encounter at inflammatory sites in vivo. EPI-hNE4 resisted hydrolysis by neutrophil matrix metalloproteases (MMPs) and serine proteases that are released from activated neutrophils in inflammatory lung secretions, including MMP-8 and MMP-9, and the elastase-related protease 3 and cathepsin G. It also resisted degradation by epithelial lung cell MMP-7 but was broken down by the Pseudomonas aeruginosa metalloelastase pseudolysin, when used in a purified system, but not when this protease competed with equimolar amounts of neutrophil elastase. We also investigated the inhibitory properties of EPI-hNE4 at the surface of purified blood neutrophils and in the sputum of cystic fibrosis patients where neutrophil elastase is in both a soluble and a gel phase. The elastase at the neutrophil surface was fully inhibited by EPI-hNE4 and formed soluble complexes. The elastase in cystic fibrosis sputum supernatants was inhibited by stoichiometric amounts of EPI-hNE4, allowing titration of the protease. But the percentage of inhibition in whole sputum homogenates varied from 50 to 100%, depending on the sample tested. EPI-hNE4 was rapidly cleaved by the digestive protease pepsin in vitro. Therefore, EPI-hNE4 seems to be an elastase inhibitor suitable for use in aerosols to treat patients with cystic fibrosis.

To investigate a potential association between occupational risk factors and severity markers of systemic sclerosis (SSc) defined by diffuse cutaneous extent, pulmonary involvement, and immunologic profile, i.e., presence of antitopoisomerase I antibody (anti-topo I).Occupational exposures were assessed in 105 patients with SSc from 1998 to 2002. Exposures to silica dust, welding fumes, solvents, and epoxy resins were investigated. A group of 39 exposed SSc patients and a group of 66 unexposed ones were identified and compared according to severity markers of SSc. The stage of cutaneous extent was defined according to the classification of Leroy, as limited scleroderma (lSSc) or diffuse scleroderma (dSSc). Respiratory status was defined by pulmonary function tests and high resolution computed tomography. Immunological profile was determined by the presence of anti-topo I or anticentromere antibodies (ACA). Statistical relationships between occupational exposures and severity markers of SSc were evaluated using a multiple correspondence analysis and Fisher's exact test.Diffuse scleroderma affected mainly patients exposed during their occupational life to toxic agents. There were significant or close to significant associations between toxic exposure and dSSc (p = 0.06), pulmonary involvement (p = 0.10), and negative ACA (p = 0.03). The most incriminated products seemed to be epoxy resins (p = 0.06), white spirit (p = 0.07), aromatic solvents (p = 0.07), and silica coupled to welding fumes (p = 0.10).Our results indicate that occupational toxic factors have an influence on the severity of SSc.

The purpose of this research was to evaluate the safety of pulmonary administration of gemcitabine and to determine the maximum tolerated dose by weekly pulmonary administrations in an animal model. Five groups of eight Wistar rats received gemcitabine at doses of 2, 4, 6, or 8 mg/kg or the vehicle solution by endotracheal spray with scintigraphic imaging of lung deposition. In order to document the safety of digestive exposure, five groups of eight rats received gemcitabine at the same dosages or the vehicle solution by gavage. Nine weekly sessions were planned, and blood cell counts and histological examinations were performed in live animals at day 64. Scintigraphic imaging confirmed pulmonary deposition in 310 of 316 spray administrations (98%) with homogeneous pattern of deposition. The maximum tolerated dose of gemcitabine by pulmonary administration was 4 mg/kg. At this dosage, administered once a week for 9 consecutive weeks, there were no chemotherapy-related deaths and no clinical, histological, or hematological signs of toxicity except for a decrease in platelet and red blood cell counts, with no clinical significance. The toxicity of gemcitabine was higher via oral than lung delivery in terms of weight loss and white blood cell toxicity at dosages of 2, 4, and 6 mg/kg. Pulmonary administration of gemcitabine is safe in rats at a maximum tolerated dose of 4 mg/kg once a week for 9 weeks. At an equivalent dosage, the toxicity of gemcitabine is lower by lung than oral administration.

Lung deposition of inhaled drugs in ventilated neonates has been studied in models of questionable relevance. With conventional nebulizers, pulmonary deposition has been limited to 1% of the total dose. The objective of this study was to assess lung delivery of aerosols in a model of neonatal ventilation using a conventional and novel electronic micropump nebulizer. Aerosol deposition studies with 99mTc diethylenetriamine pentaacetate (99mTc-DTPA) were performed in four macaques (2.6 kg) that were ventilated through a 3.0-mm endotracheal tube (with neonatal settings (peak inspiratory pressure 12-14 mbar, positive end-expiratory pressure 2 mbar, I/E ratio 1/2, respiratory rate 40/min), comparing a jet-nebulizer MistyNeb (3-mL charge, 4.8 microm), an electronic micropump nebulizer operating continuously [Aeroneb Professional Nebulizer (APN-C); 0.5-mL charge, 4.6 microm], and another synchronized with inspiration [Aeroneb Professional Nebulizer Synchronized (APN-S); 0.5-mL charge, 2.8 microm]. The amount of radioactivity deposited into lungs and connections and remaining in the nebulizer was measured by a gamma counter. Despite similar amounts of 99mTc-DTPA in the respiratory circuit with all nebulizers, both APN-S and APN-C delivered more drug to the lungs than MistyNeb (14.0, 12.6, and 0.5% in terms of percentage of nebulizer charge, respectively; p = 0.006). Duration of delivery was shorter with APN-C than with the two other nebulizers (2 versus 6 and 10 min for the APN-S and the MistyNeb, respectively; p < 0.001). Electronic micropump nebulizers are more efficient to administer aerosols in an animal model of ventilated neonates. Availability of Aerogen's electronic micropump nebulizers offers new opportunities to study clinical efficacy and risks of aerosol therapy in ventilated neonates.

Resume Les atteintes cardiorespiratoires de la maladie de Still de l’adulte (MSA) sont moins connues que les atteintes cutanees et articulaires. L’atteinte pleuropericardique est la plus frequente. Les autres manifestations cardiorespiratoires, qui peuvent accompagner ou reveler la maladie, sont de diagnostic plus difficile mais doivent cependant etre rapidement reconnues car elles peuvent etre vitales. Toutefois, leur pronostic a ete transforme par les nouveaux immunosuppresseurs. La pathogenie est incertaine mais fait intervenir avant tout des mecanismes immunologiques. Les cytokines pro-inflammatoires, au premier rang desquelles l’interleukine 1 (IL1), jouent un role pivot, notamment dans l’activation macrophagique, qui est centrale dans la physiopathologie de la MSA. Les manifestations cardiorespiratoires sont classees en tenant compte de l’anatomie. Les atteintes cardiaques peuvent interesser l’ensemble des tuniques et l’artere pulmonaire. Les atteintes respiratoires concernent la plevre, le parenchyme pulmonaire (pneumopathie organisee, pneumopathie interstitielle diffuse, syndrome de detresse respiratoire aigue, amylose), les muscles, dont le diaphragme. Enfin, certaines manifestations peuvent etre liees au traitement. La corticotherapie est le traitement de reference. Elle est tres efficace dans l’atteinte pleuropericardique. Le methotrexate est prescrit en cas de resistance ou d’inefficacite des corticoides. Les biotherapies, au premier rang desquelles les antagonistes de l’IL1 et de l’IL6, ont transforme le pronostic des formes resistantes a ces molecules.

The aim of this study was to assess a residual gravimetric method based on weighing dry filters to measure the aerosol output of nebulizers. This residual gravimetric method was compared to assay methods based on spectrophotometric measurement of terbutaline (Bricanyl, Astra Zeneca, France), high-performance liquid chromatography (HPLC) measurement of tobramycin (Tobi, Chiron, U.S.A.), and electrochemical measurements of NaF (as defined by the European standard). Two breath-enhanced jet nebulizers, one standard jet nebulizer, and one ultrasonic nebulizer were tested. Output produced by the residual gravimetric method was calculated by weighing the filters both before and after aerosol collection and by filter drying corrected by the proportion of drug contained in total solute mass. Output produced by the electrochemical, spectrophotometric, and HPLC methods was determined after assaying the drug extraction filter. The results demonstrated a strong correlation between the residual gravimetric method (x axis) and assay methods (y axis) in terms of drug mass output (y = 1.00 x -0.02, r(2) = 0.99, n = 27). We conclude that a residual gravimetric method based on dry filters, when validated for a particular agent, is an accurate way of measuring aerosol output.

The use of recombinant GM-CSF in the treatment of pulmonary alveolar proteinosis (PAP) has been reported recently in Thorax 1,2 in cases with anti-GM-CSF antibodies. We report the successful use of GM-CSF in a patient with no GM-CSF antibodies, which provides further evidence for considering GM-CSF as a possible keystone to the treatment of PAP. A 35 year old man with a past history of idiopathic marrow aplasia treated with antilymphocytic serum in 1983 and Mycobacterium avium systemic infection presented in February 1999 with a 4 month history of dyspnoea. A diagnosis of PAP was suspected from the HRCT scan which showed …

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.

The role of inhaled iloprost should be suspected in cases of gastro-intestinal haemorrhage in patients suffering from pulmonary hypertension (PH) receiving this treatment, and the way the drug is administered should possibly be changed. Clinical, functional and haemodynamic deterioration of systemic scleroderma-PH in a 73-year-old Caucasian woman without any other past medical history, led to the introduction of aerosolized iloprost 5 µg six times a day in addition to her existing treatment of sitaxentan 100 mg once daily, sildenafil 20 mg three times daily, furosemide 40 mg once daily, bromazepam 6 mg one to two times daily, calcium 1000 mg once daily, cholecalciferol 880 IU once daily, monosodic alendronate 70 mg weekly, fluindione 20 mg once daily with an international normalized ratio (INR) maintained between 2 and 3. In the past, she had had occasional melaena, once a month, generally the day following alendronate ingestion. Two months after beginning aerosolized iloprost, the frequency of her melaena increased, becoming continuous, after each aerosolization (INR = 2.18). An oesogastroduodenal endoscopy revealed digestive angiomatosis, and the hypothesis that iloprost could play a role in causing this lesion to bleed was raised. As reassessment of pulmonary hypertension suggested the benefit of inhaled iloprost, it was decided to reduce the regimen to five aerosols a day, avoiding the first post-prandial hour. The frequency of melaena decreased and abdominal meteorism stopped completely. Reducing the dose of aerosols did not have any effect on the PH at the next reassessment. In a 79-year-old Caucasian man with a past medical history of ischaemic cardiomyopathy, inhaled iloprost aerosol 5 µg six times a day was initiated following deterioration of a PH secondary to a chronic obstructive pulmonary disease, in association with previous treatment with sildenafil 20 mg three times daily, bosentan 125 mg two times daily, fluindione 20 mg once daily (INR between 2 and 3 throughout follow-up), furosemide 40 mg once daily, amiodarone 200 mg once daily, pravastatin 40 mg once daily, ramipril 5 mg once daily, clopidogrel 75 mg once daily, tiotropium bromide 1 inhalation day−1, molsidomine 2 mg three times daily and potassium chloride 600 mg day−1. One month earlier, anaemia with iron deficiency had been diagnosed and treated by blood transfusion and ferrous sulphate supplements (80 mg two times daily). Oesogastroduodenal endoscopy had revealed millimetric bleeding angiodysplasias in the duodenal cap, which had been treated by argon plasma coagulation. Four months after beginning inhaled iloprost, haemoglobinaemia was 85 g l−1 with iterative digestive haemorrhages requiring several blood transfusions, despite ongoing ferrous supplementation. A colonoscopy found a 3 mm caecal angiodysplasia and two colic polyps requiring argon plasma coagulation therapy and polypectomy. In spite of this digestive procedure, gastro-intestinal haemorrhage continued and consequently clopidogrel was stopped and iloprost reduced to 5 aerosols a day, avoiding the immediate post-prandial period. There was no recurrence of digestive bleeding and haemoglobin stabilized. At the next reassessment, there had been no worsening of PH. These two cases suggest a possible link between digestive haemorrhage and iloprost aerosols. There was a temporal relationship between inhalation of iloprost and the onset or worsening of bleeding, and between the reduced dose of iloprost inhalation and improvement of bleeding symptoms. The digestive haemorrhage did not recur after the iloprost dosage was reduced and inhalation was avoided after meals. The role of fluindione can be excluded because the INR did not increase and because bleeding symptoms improved despite the continuation of fluindione treatment. In the second patient, stopping clopidogrel may have had a beneficial effect on gastro-intestinal haemorrhage, but the symptoms worsened when iloprost was started, requiring blood transfusion. The role of other drugs can be ruled out as bleeding symptoms improved despite the continuation of these drugs. Neither of these patients had any history of liver disease. The evidence for the effect of inhaled iloprost on digestive bleeding is strong and possibly multifactorial. Iloprost is an analogue of epoprostenol. Besides its vasodilatory effect, it inhibits platelet function in a dose-related manner and platelet aggregability returns to baseline levels after the end of the infusion [1]. Because its absolute bioavailability is approximately 80% [2], inhaled iloprost may induce sufficiently high serum concentrations to produce adverse systemic effects. Splanchnic blood flow increases after iloprost administration [3], which could promote the bleeding of an angioma. This pharmacodynamic effect could also explain why bleeding symptoms improved when iloprost was no longer inhaled close to meals. It is possible that part of the aerosolized iloprost is swallowed rather than truly inhaled and could have a direct action on the digestive cell wall. Prostaglandins inhibit secretion of histamine and pancreastatin by enterochromaffin-like cells of the gastric epithelium and therefore decrease gastric acidity, making the hypothesis that digestive haemorrhage is related to gastro-duodenal ulcers highly improbable [4]. In conclusion, these observations suggest that patients with a risk of digestive bleeding should avoid inhaled aerosols during peri-prandial periods as far as possible, and that patients with a history of digestive bleeding should be monitored clinically and biologically during the months following the introduction of inhaled iloprost.