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Topic:Lung Health

Lung health in horses encompasses the study of respiratory system function, disease, and maintenance in equine species. The equine respiratory system is vital for oxygen exchange and plays a significant role in overall health and athletic performance. Conditions affecting lung health include inflammatory airway disease (IAD), recurrent airway obstruction (RAO), and exercise-induced pulmonary hemorrhage (EIPH). These conditions can impact a horse's respiratory efficiency and performance capabilities. Research in this area often focuses on understanding the pathophysiology, diagnosis, and management of respiratory diseases, as well as the impact of environmental factors on lung function. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, diagnostic approaches, and therapeutic strategies related to lung health in horses.
Glucocorticosteroids administration is associated with increased regulatory T cells in equine asthmatic lungs.
Veterinary immunology and immunopathology    May 24, 2018   Volume 201 67-71 doi: 10.1016/j.vetimm.2018.05.010
Boivin R, Vargas A, Cano P, Lavoie JP.Recurrent inflammation in severe equine asthma causes a remodeling of the airways leading to incompletely reversible airway obstruction. Despite the improvement of clinical signs and lung function with glucocorticoids (GC), inflammation, translated by an increased percentage of neutrophils, persists in the airways. Regulatory T cells (Treg) have been shown to have anti-inflammatory properties and play an important role in balancing the immune response by suppressing effector lymphocyte activity. However, interactions between Treg, neutrophils and glucocorticosteroids in vivo are unclear, parti...
Use of Nasotracheal Intubation during General Anesthesia in Two Ponies with Tracheal Collapse.
Frontiers in veterinary science    March 13, 2018   Volume 5 42 doi: 10.3389/fvets.2018.00042
Ida KK, Sauvage A, Gougnard A, Grauwels M, Serteyn D, Sandersen C.Ponies with tracheal collapse may have an increased anesthetic risk due to airway obstruction during induction and recovery. To our knowledge, there are no anesthetic descriptions of these patients, despite a reported 5.6% incidence and 77% mortality rate. Two Shetland ponies with tracheal collapse, a 12-year-old male (pony 1) and a 27-year-old female (pony 2), were referred for right eye enucleation due to a perforating corneal ulcer and severe recurrent uveitis, respectively. Pony 1 was stressed, had lung stridor and hyperthermia, and developed inspiratory dyspnea with handling. Radiography ...
Influence of bronchoalveolar lavage on thoracic radiography in the horse.
Journal of veterinary science    February 28, 2018   Volume 19, Issue 4 563-569 doi: 10.4142/jvs.2018.19.4.563
Barton AK, Schulze T, Doherr MG, Gehlen H.Bronchoalveolar lavage (BAL) and thoracic radiography are routinely performed diagnostic procedures. We hypothesized that BAL increases the interstitial opacity of caudoventral and caudodorsal thoracic radiographs. Fifty-three horses, including 8 clinic owned and 45 from a referral hospital population, were classified as healthy controls (n = 12), severe equine asthma (recurrent airway obstruction, n = 12) or mild-to-moderate equine asthma (inflammatory airway disease, n = 21) based on the results of a clinical scoring system. Eight were excluded due to different diagnoses and poor image quali...
Effect of a syringe aspiration technique versus a mechanical suction technique and use of N-butylscopolammonium bromide on the quantity and quality of bronchoalveolar lavage fluid samples obtained from horses with the summer pasture endophenotype of equine asthma.
American journal of veterinary research    February 22, 2018   Volume 79, Issue 3 348-355 doi: 10.2460/ajvr.79.3.348
Bowser JE, Costa LRR, Rodil AU, Lopp CT, Johnson ME, Wills RW, Swiderski CE.OBJECTIVE To evaluate the effect of 2 bronchoalveolar lavage (BAL) sampling techniques and the use of N-butylscopolammonium bromide (NBB) on the quantity and quality of BAL fluid (BALF) samples obtained from horses with the summer pasture endophenotype of equine asthma. ANIMALS 8 horses with the summer pasture endophenotype of equine asthma. PROCEDURES BAL was performed bilaterally (right and left lung sites) with a flexible videoendoscope passed through the left or right nasal passage. During lavage of the first lung site, a BALF sample was collected by means of either gentle syringe aspirati...
Histologic investigation of airway inflammation in postmortem lung samples from racehorses.
American journal of veterinary research    February 22, 2018   Volume 79, Issue 3 342-347 doi: 10.2460/ajvr.79.3.342
Ter Woort F, Caswell JL, Arroyo LG, Viel L.OBJECTIVE To describe histologic findings in the small airways during postmortem examination of actively racing horses and to quantify the degree of airway inflammation by use of a semiquantitative scoring system. SAMPLE Lung tissues obtained from 95 horses (Thoroughbreds, Standardbreds, and Quarter Horses) that had been actively racing or training. PROCEDURES 10 standardized lung sections were obtained during postmortem examination of 37 horses that had been actively racing or training, and 2 histologic sections of the caudodorsal lung lobes previously collected from each of 58 horses that di...
Modeling asthma: Pitfalls, promises, and the road ahead.
Journal of leukocyte biology    February 16, 2018   Volume 104, Issue 1 41-48 doi: 10.1002/JLB.3MR1117-436R
Rosenberg HF, Druey KM.Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines. Recent models of disease induction have advanced to include physiologic aero...
Development of septic polysynovitis and uveitis in foals experimentally infected with Rhodococcus equi.
PloS one    February 7, 2018   Volume 13, Issue 2 e0192655 doi: 10.1371/journal.pone.0192655
Huber L, Giguère S, Berghaus LJ, Hanafi A, Vitosh-Sillman S, Czerwinski SL.Rhodococcus equi is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with R. equi and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with R. equi and to determine if these disorders are the direct res...
Bronchoalveolar lavage fluid neutrophilia is associated with the severity of pulmonary lesions during equine asthma exacerbations.
Equine veterinary journal    February 7, 2018   Volume 50, Issue 5 609-615 doi: 10.1111/evj.12806
Bullone M, Joubert P, Gagné A, Lavoie JP, Hélie P.The severe form of equine asthma is associated with pathological changes of the peripheral airways and pulmonary parenchyma that are only partly described. Also, the relationship between these structural alterations and the percentage of neutrophils found within the airway lumen, assessed by bronchoalveolar lavage fluid (BALF) cytology, remains ill-defined. Objective: To examine the histological lesions associated with equine asthma during disease exacerbation and remission, and their relationship with lung function and BALF neutrophilia. Methods: Observational retrospective study. Methods: Pe...
Equine neutrophils and their role in ischemia reperfusion injury and lung inflammation.
Cell and tissue research    January 15, 2018   Volume 371, Issue 3 639-648 doi: 10.1007/s00441-017-2770-1
Anderson SL, Singh B.Horses are susceptible to a multitude of inflammatory conditions that are characterized by a strong neutrophilic response. Here, we review basic equine neutrophil biology and explore the role of neutrophils in inflammatory conditions with emphasis on intestinal ischemia and reperfusion injury and lung inflammation. In addition, unique aspects of equine neutrophil biology have been highlighted. Neutrophils comprise the highest proportion of circulating white blood cells in equine blood. The concentration of circulating equine neutrophils is a primary indicator of systemic inflammation. Addition...
Maintenance of equine anaesthesia over the last 50 years: Controlled inhalation of volatile anaesthetics and pulmonary ventilation.
Equine veterinary journal    January 8, 2018   Volume 50, Issue 3 282-291 doi: 10.1111/evj.12793
Mosing M, Senior JM.In the first edition of this journal, Barbara Weaver wrote a review titled 'Equine Anaesthesia', stating that, at that time, it was quickly becoming accepted practice that many horses were being anaesthetised 'by essentially similar procedures, i.e. premedication, induction and then maintenance by controlled inhalation'. To celebrate the 50th anniversary of the first edition of this journal, this review covers the development of understanding and practice of inhalational anaesthesia and controlled ventilation in horses over the last 50 years. We review how the perceived benefits of halothane ...
Intestinal and hepatic contributions to the pharmacokinetic interaction between gamithromycin and rifampicin after single-dose and multiple-dose administration in healthy foals.
Equine veterinary journal    January 8, 2018   Volume 50, Issue 4 525-531 doi: 10.1111/evj.12796
Berlin S, Wallstabe S, Scheuch E, Oswald S, Hasan M, Wegner D, Grube M, Venner M, Ullrich A, Siegmund W.Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative. Objective: To evaluate the pharmacokinetic ...
Comparative View of Lung Vascular Endothelium of Cattle, Horses, and Water Buffalo.
Advances in anatomy, embryology, and cell biology    December 31, 2017   Volume 228 21-39 doi: 10.1007/978-3-319-68483-3_2
Schneberger D, Sethi RS, Singh B.Endothelium plays an important role in maintaining the vascular barrier and physiological homeostasis. Endothelium also is fundamental to the initiation and regulation of inflammation. Endothelium demonstrates phenotypic and functional heterogeneity not only among various organs but also within an organ. One of the striking examples would be the pulmonary endothelium that participates in creating blood-air barrier. Endothelium in large pulmonary blood vessels is distinct in structure and function from that lining of the pulmonary capillaries. This chapter focuses on the comparative aspects of ...
Horses With Pasture Asthma Have Airway Remodeling That Is Characteristic of Human Asthma.
Veterinary pathology    December 20, 2017   Volume 55, Issue 1 144-158 doi: 10.1177/0300985817741729
Ferrari CR, Cooley J, Mujahid N, Costa LR, Wills RW, Johnson ME, Swiderski CE.Severe equine asthma, formerly recurrent airway obstruction (RAO), is the horse counterpart of human asthma, affecting horses maintained indoors in continental climates. Equine pasture asthma, formerly summer pasture RAO, is clinically similar but affects grazing horses during hot, humid conditions in the southeastern United States and United Kingdom. To advance translational relevance of equine pasture asthma to human asthma, histologic features of airway remodeling in human asthma were scored in lung lobes from 15 pasture asthma-affected and 9 control horses of mixed breeds. All noncartilagi...
Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma.
Respiratory research    December 12, 2017   Volume 18, Issue 1 207 doi: 10.1186/s12931-017-0689-4
Vargas A, Boivin R, Cano P, Murcia Y, Bazin I, Lavoie JP.Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway. Six neutrophilic severe asthmatic horses and six healthy controls were studied while being treated...
Characterization of respiratory dendritic cells from equine lung tissues.
BMC veterinary research    November 6, 2017   Volume 13, Issue 1 313 doi: 10.1186/s12917-017-1240-z
Lee Y, Kiupel M, Soboll Hussey G.Dendritic cells (DCs) are professional antigen-presenting cells that have multiple subpopulations with different phenotypes and immune functions. Previous research demonstrated that DCs have strong potential for anti-viral defense in the host. However, viruses including alphaherpesvirinae have developed strategies to interfere with the function or maturation of DCs, causing immune dysfunction and avoidance of pathogen elimination. The goal of the present study was to isolate and characterize equine lung-derived DCs (L-DCs) for use in studies of respiratory viruses and compare their features wi...
Pulmonary disposition and pharmacokinetics of minocycline in adult horses.
American journal of veterinary research    October 28, 2017   Volume 78, Issue 11 1319-1328 doi: 10.2460/ajvr.78.11.1319
Echeverria KO, Lascola KM, Giguère S, Foreman JH, Austin SA.OBJECTIVE To determine pharmacokinetics and pulmonary disposition of minocycline in horses after IV and intragastric administration. ANIMALS 7 healthy adult horses. PROCEDURES For experiment 1 of the study, minocycline was administered IV (2.2 mg/kg) or intragastrically (4 mg/kg) to 6 horses by use of a randomized crossover design. Plasma samples were obtained before and 16 times within 36 hours after minocycline administration. Bronchoalveolar lavage (BAL) was performed 4 times within 24 hours after minocycline administration for collection of pulmonary epithelial lining fluid (PELF) and BAL ...
Expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 and -9 in horses with chronic airway inflammation.
American journal of veterinary research    October 28, 2017   Volume 78, Issue 11 1329-1337 doi: 10.2460/ajvr.78.11.1329
Rossi HS, Koho NM, Ilves M, Rajamäki MM, Mykkänen AK.OBJECTIVE To examine whether expression of extracellular matrix metalloproteinase inducer (EMMPRIN) can be detected in equine lungs and whether it correlates with matrix metalloproteinase (MMP)-2 and -9 expression in bronchoalveolar lavage fluid (BALF) of horses with chronic inflammation of the lungs (ie, lower airway inflammation [LAI]). ANIMALS 29 horses with signs of chronic respiratory tract disease, which were classified as the LAI (n = 17) and LAI with respiratory distress (RDLAI [12]) groups, and 15 control horses. PROCEDURES BALF, tracheal aspirate, and blood samples were obtained, and...
Upper and lower respiratory tract microbiota in horses: bacterial communities associated with health and mild asthma (inflammatory airway disease) and effects of dexamethasone.
BMC microbiology    August 23, 2017   Volume 17, Issue 1 184 doi: 10.1186/s12866-017-1092-5
Bond SL, Timsit E, Workentine M, Alexander T, Léguillette R.The microbial composition of the equine respiratory tract, and differences due to mild equine asthma (also called Inflammatory Airway Disease (IAD)) have not been reported. The primary treatment for control of IAD in horses are corticosteroids. The objectives were to characterize the upper and lower respiratory tract microbiota associated with respiratory health and IAD, and to investigate the effects of dexamethasone on these bacterial communities using high throughput sequencing. Results: The respiratory microbiota of horses was dominated by four major phyla, Proteobacteria (43.85%), Actinob...
Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma.
Scientific reports    August 18, 2017   Volume 7, Issue 1 8843 doi: 10.1038/s41598-017-09414-8
Bullone M, Vargas A, Elce Y, Martin JG, Lavoie JP.Asthmatic airways are inflamed and undergo remodelling. Inhaled corticosteroids and long-acting β2-agonist combinations are more effective than inhaled corticosteroid monotherapy in controlling disease exacerbations, but their effect on airway remodelling and inflammation remains ill-defined. This study evaluates the contribution of inhaled fluticasone and salmeterol, alone or combined, to the reversal of bronchial remodelling and inflammation. Severely asthmatic horses (6 horses/group) were treated with fluticasone, salmeterol, fluticasone/salmeterol, or with antigen avoidance for 12 weeks. ...
Age associated changes in peripheral airway smooth muscle mass of healthy horses.
Veterinary journal (London, England : 1997)    August 5, 2017   Volume 226 62-64 doi: 10.1016/j.tvjl.2017.07.007
Bullone M, Pouyet M, Lavoie JP.Peripheral airway smooth muscle (ASM) mass is increased in severe equine asthma, but no information is available on age related changes in ASM. In this study, peripheral ASM dimensions were determined in healthy horses of different ages. The thickness of the peripheral ASM layer was constant in horses of different ages, but ASM occupied a greater proportion of the inner wall area in young horses compared to older horses. This finding suggests that equine airways experience a decrease in the relative abundance of ASM with age.
Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis.
Frontiers in medicine    July 28, 2017   Volume 4 118 doi: 10.3389/fmed.2017.00118
Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis-though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients w...
Regional ventilation distribution and dead space in anaesthetized horses treated with and without continuous positive airway pressure: novel insights by electrical impedance tomography and volumetric capnography.
Veterinary anaesthesia and analgesia    July 3, 2017   Volume 45, Issue 1 31-40 doi: 10.1016/j.vaa.2017.06.004
Mosing M, Auer U, MacFarlane P, Bardell D, Schramel JP, Böhm SH, Bettschart-Wolfensberger R, Waldmann AD.The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) on regional distribution of ventilation and dead space in anaesthetized horses. Methods: Randomized, experimental, crossover study. Methods: A total of eight healthy adult horses. Methods: Horses were anaesthetized twice with isoflurane in 50% oxygen and medetomidine as continuous infusion in dorsal recumbency, and administered in random order either CPAP (8 cmHO) or NO CPAP for 3 hours. Electrical impedance tomography (and volumetric capnography (VCap) measurements were performed every 30 minutes. L...
Effect of Dexamethasone and Fluticasone on Airway Hyperresponsiveness in Horses With Inflammatory Airway Disease.
Journal of veterinary internal medicine    May 31, 2017   Volume 31, Issue 4 1193-1201 doi: 10.1111/jvim.14740
Léguillette R, Tohver T, Bond SL, Nicol JA, McDonald KJ.Airway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC R ) or hyperreactivity (slope of the histamine dose-response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD. Objective: To determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 μg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD. Methods: A randomized crossover study design was used. Eight horses with IAD were assign...
The Horse-Racing Effect and Lung Function: Can We Slow the Fastest Horse?
American journal of respiratory and critical care medicine    May 2, 2017   Volume 195, Issue 9 1134-1135 doi: 10.1164/rccm.201703-0540ED
Berry CE, Drummond MB.No abstract available
Pharmacological treatments in asthma-affected horses: A pair-wise and network meta-analysis.
Equine veterinary journal    April 9, 2017   Volume 49, Issue 6 710-717 doi: 10.1111/evj.12680
Calzetta L, Roncada P, di Cave D, Bonizzi L, Urbani A, Pistocchini E, Rogliani P, Matera MG.Equine asthma is a disease characterised by reversible airflow obstruction, bronchial hyper-responsiveness and airway inflammation following exposure of susceptible horses to specific airborne agents. Although clinical remission can be achieved in a low-airborne dust environment, repeated exacerbations may lead to irreversible airway remodelling. The available data on the pharmacotherapy of equine asthma result from several small studies, and no head-to-head clinical trials have been conducted among the available medications. Objective: To assess the impact of the pharmacological interventions...
Comparison of Thoracic Ultrasonography and Radiography for the Detection of Induced Small Volume Pneumothorax in the Horse. Partlow J, David F, Hunt LM, Relave F, Blond L, Pinilla M, Lavoie JP.Small volume pneumothorax can be challenging to diagnose in horses. The current standard method for diagnosis is standing thoracic radiography. We hypothesized that thoracic ultrasonography would be more sensitive. Objectives of this prospective, experimental study were to describe a thoracic ultrasound method for detection of small volume pneumothorax in horses and to compare results of radiography and ultrasound in a sample of horses with induced small volume pneumothorax. Six mature healthy horses were recruited for this study. For each horse, five 50 ml air boluses were sequentially introd...
Evaluation of contractile phenotype in airway smooth muscle cells isolated from endobronchial biopsy and tissue specimens from horses.
American journal of veterinary research    February 28, 2017   Volume 78, Issue 3 359-370 doi: 10.2460/ajvr.78.3.359
Vargas A, Peltier A, Dubé J, Lefebvre-Lavoie J, Moulin V, Goulet F, Lavoie JP.OBJECTIVE To develop a method to maintain the initial phenotype of airway smooth muscle (ASM) cells isolated from equine endobronchial biopsy specimens in long-term cell culture. SAMPLE Endobronchial tissue specimens (8 to 10/horse) collected from the lungs of previously healthy horses at necropsy (n = 12) and endobronchial biopsy specimens collected from standing, sedated, heaves-affected horses in clinical remission of the disease (5) and control horses (4). PROCEDURES A sampling protocol was developed to recover and maintain a contractile phenotype in ASM cells from endobronchial specimens ...
Pharmacological indices and pulmonary distribution of rifampicin after repeated oral administration in healthy foals.
Equine veterinary journal    February 25, 2017   Volume 49, Issue 5 618-623 doi: 10.1111/evj.12662
Berlin S, Kirschbaum A, Spieckermann L, Oswald S, Keiser M, Grube M, Venner M, Siegmund W.The treatment of equine lung infections by Rhodococcus equi with rifampicin is empirically based because pharmacokinetic/pharmacodynamic (PK/PD) indices and pivotal clinical outcome data are not available. Objective: To evaluate the pharmacokinetics and pulmonary distribution of rifampicin into epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALC) to predict antimicrobial activity in the lung using PK/PD indices. Methods: Controlled, randomised, two-period, crossover, repeated-dose study with an initial arm to measure disposition after i.v. administration of rifampicin. Methods...
Regional distribution of ventilation in horses in dorsal recumbency during spontaneous and mechanical ventilation assessed by electrical impedance tomography: a case series.
Veterinary anaesthesia and analgesia    February 23, 2017   Volume 44, Issue 1 127-132 doi: 10.1111/vaa.12405
Mosing M, Marly-Voquer C, MacFarlane P, Bardell D, Böhm SH, Bettschart-Wolfensberger R, Waldmann AD.To evaluate the regional distribution of ventilation in horses during spontaneous breathing and controlled mechanical ventilation (CMV) using electrical impedance tomography (EIT). Methods: Prospective, experimental case series. Methods: Four anaesthetized experimental horses. Methods: Horses were anaesthetized with isoflurane in an oxygen-air mixture and medetomidine continuous rate infusion, placed in dorsal recumbency with an EIT belt around the thorax, and allowed to breathe spontaneously until PaCO reached 13.3 kPa (100 mmHg), when volume CMV was started. For each horse, the EIT signal wa...
Bronchopulmonary pharmacokinetics of (R)-salbutamol and (S)-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses.
British journal of clinical pharmacology    February 8, 2017   Volume 83, Issue 7 1436-1445 doi: 10.1111/bcp.13228
Jacobson GA, Raidal S, Robson K, Narkowicz CK, Nichols DS, Haydn Walters E.Salbutamol is usually administered as a racemic mixture but little is known about the enantioselectivity of salbutamol pharmacokinetics in the lung. This study was designed to investigate enantiomer concentrations in lung tissue after inhaled dosing. Horses (n = 12) received racemic salbutamol 1000 μg via inhalation. Enantioselective ultra performance liquid chromatography-tandem mass spectrometry was used to determine salbutamol concentrations in pulmonary epithelial lining fluid (PELF) sampled 2, 5, 10 and 15 min after administration, in central lung (endoscopic bronchial biopsy) and per...