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To relate exposure to adverse health effects, it is necessary to know where particles in the submicron range deposit in the respiratory tract. The possibly higher vulnerability of children requires specific inhalation studies. However, radio-aerosol deposition experiments involving children are rare because of ethical restrictions related to radiation exposure. Thus, an in vivo study was conducted using three baboons as a child respiratory tract model to assess regional deposition patterns (thoracic region vs. extrathoracic region) of radioactive polydisperse aerosols ([d16–d84], equal to [0.15 µm–0.5 µm], [0.25 µm–1 µm], or [1 µm–9 µm]). Results clearly demonstrated that aerosol deposition within the thoracic region and the extrathoraic region varied substantially according to particle size. High deposition in the extrathoracic region was observed for the [1 µm–9 µm] aerosol (72%±17%). The [0.15 µm–0.5 µm] aerosol was associated almost exclusively with thoracic region deposition (84%±4%). Airborne particles in the range of [0.25 µm–1 µm] showed an intermediate deposition pattern, with 49%±8% in the extrathoracic region and 51%±8% in the thoracic region. Finally, comparison of baboon and human inhalation experiments for the [1 µm–9 µm] aerosol showed similar regional deposition, leading to the conclusion that regional deposition is species-independent for this airborne particle sizes. [ABSTRACT FROM AUTHOR]

Purpose: Intranasal deposition of aerosols is often studied using in vitro nasal cavity models. However, the relevance of these models to predict in vivo human deposition has not been validated. This study compared in vivo nasal aerosol deposition and in vitro deposition in a human plastinated head model (NC1) and its replica constructed from CT-scan (NC2). Methods: Two nebulizers (Atomisor Sonique® and Easynose®) were used to administer a 5.6 μm aerosol of Tc-DTPA to seven healthy volunteers and to the nasal models. Aerosol deposition was quantified by γ-scintigraphy in the nasal, upper nasal cavity and maxillary sinus (MS) regions. The distribution of aerosol deposition was determined along three nasal cavity axes (x, y and z). Results: There was no significant difference regarding aerosol deposition between the volunteers and NC1. Aerosol deposition was significantly lower in NC2 than in volunteers regarding nasal region ( p < 0.05) but was similar for the upper nasal cavity and MS regions. Mean aerosol distribution for NC1 came within the standard deviation (SD) of in vivo distribution, whereas that of NC2 was outside the in vivo SD for x and y axes. Conclusions: In conclusion, nasal models can be used to predict aerosol deposition produced by nebulizers, but their performance depends on their design. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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[F]fluoro- d-glucose positron emission tomography (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 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 F-FDG PET did not reveal the previous abnormal tracheal 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. 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 F-FDG PET for tracheal involvement of UC, allowing a non-invasive assessment of local inflammation. [ABSTRACT FROM AUTHOR]

Nebulized antibiotic therapy directly targets airways and lung parenchyma resulting in high local concentrations and potentially lower systemic toxicities. Experimental and clinical studies have provided evidence for elevated lung concentrations and rapid bacterial killing following the administration of nebulized antibiotics during mechanical ventilation. Delivery of high concentrations of antibiotics to infected lung regions is the key to achieving efficient nebulized antibiotic therapy. However, current non-standardized clinical practice, the difficulties with implementing optimal nebulization techniques and the lack of robust clinical data have limited its widespread adoption. The present review summarizes the techniques and clinical constraints for optimal delivery of nebulized antibiotics to lung parenchyma during invasive mechanical ventilation. Pulmonary pharmacokinetics and pharmacodynamics of nebulized antibiotic therapy to treat ventilator-associated pneumonia are discussed and put into perspective. Experimental and clinical pharmacokinetics and pharmacodynamics support the use of nebulized antibiotics. However, its clinical benefits compared to intravenous therapy remain to be proved. Future investigations should focus on continuous improvement of nebulization practices and techniques. Before expanding its clinical use, careful design of large phase III randomized trials implementing adequate therapeutic strategies in targeted populations is required to demonstrate the clinical effectiveness of nebulized antibiotics in terms of patient outcomes and reduction in the emergence of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Colistin, administered as the prodrug colistin methanesulphonate (CMS), is an antibiotic frequently administered as aerosol in cystic fibrosis (CF) patient. Our aim was to assess the plasma PK of colistin in CF patients treated with CMS administered intravenously or as aerosol and to compare these results with those previously reported in healthy volunteers. Six CF patients were included, CMS and colistin concentrations were measured in plasma, urine and sputum. Either after single intravenous administration of 2 Million International Unit (MIU) or after repeated nebulizations of 2 MIU of CMS. PK of CMS and colistin were assessed by a mixed effect modeling approach. Renal clearance of CMS was lower in CF patients compared to that previously reported in healthy volunteers (64.3 mL/min (RSE = 15%) vs. 103 mL/min (RSE = 8%)). However, apparent clearance of colistin was higher in CF patients compared to healthy volunteers (124 mL/min (RSE = 13%) vs. 48.7 mL/min (RSE = 15%)), resulting in reduced systemic exposure to colistin (dose normalized AUC (2 MIU) of 7.4 h.mg/L/MIU vs. 11.2 h.mg/L/MIU). After repeated nebulizations, colistin concentrations were very low in plasma (<0.21 mg/L). Although our study suggests a lower median dose normalized colistin plasma concentrations in CF patients compared with healthy controls, this difference was not significant and a larger study is needed to substantiate this. • Colistin systemic exposure in CF patients seems to be reduced compared to healthy volunteers after IV administration of CMS • Effective concentrations of colistin should be difficult to reach in CF patients after IV administration of CMS • After repeated nebulizations of CMS in CF patients, colistin concentrations vary but are always relatively high in sputum [ABSTRACT FROM AUTHOR]