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Summary Reasons for performing study Agreement between airway reactivity measured by flowmetric plethysmography and histamine bronchoprovocation, and lower airway inflammation measured by bronchoalveolar lavage (BAL) cytology, has not been studied in horses with suspected inflammatory airway disease (IAD). Objectives We tested the hypothesis that airway reactivity is associated with BAL cytology in horses presenting for unexplained poor performance and/or chronic cough. Study design Prospective clinical study. Methods Forty-five horses, predominantly young Standardbred racehorses, presenting for unexplained poor performance or chronic cough, underwent endoscopic evaluation, tracheal wash, flowmetric plethysmography with histamine bronchoprovocation and BAL. Histamine response was measured by calculating PC35, the concentration of nebulised histamine eliciting an increase in Δflow of 35%. Results In this population, there was no significant correlation between histamine response and cell populations in BAL cytology. When airway hyperreactivity (AHR) was defined as ≥35% increase in Δflow at a histamine concentration of

REASONS FOR PERFORMING STUDY In clinical practice, veterinarians often depend on owner-reported signs to assess the clinical course of horses with recurrent airway obstruction (RAO). OBJECTIVES To test whether owner-reported information on frequency of coughing and observation of nasal discharge are associated with clinical, cytological and bronchoprovocation findings in RAO-affected horses in nonstandardised field conditions. STUDY DESIGN Cross-sectional study comparing healthy and RAO-affected horses. METHODS Twenty-eight healthy and 34 RAO-affected Swiss Warmblood horses were grouped according to owner-reported 'coughing frequency' and 'nasal discharge'. Differences between these groups were examined using clinical examination, blood gas analyses, endoscopic mucus scores, cytology of tracheobronchial secretion and bronchoalveolar lavage fluid, and airway hyperresponsiveness determined by plethysmography with histamine bronchoprovocation. RESULTS Frequently coughing horses differed most markedly from healthy control animals. Histamine bronchoprovocation-derived parameters were significantly different between the healthy control group and all RAO groups. Mucus grades and tracheobronchial secretion and bronchoalveolar lavage fluid neutrophil percentages had particularly high variability, with overlap of findings between groups. Owner satisfaction with the clinical status of the horse was high, even in severely affected horses. CONCLUSIONS Owner-reported coughing and nasal discharge are associated with specific clinical and diagnostic findings in RAO-affected horses in field settings. While airway hyperresponsiveness differentiates best between healthy horses and asymptomatic RAO-affected horses, the absence of coughing and nasal discharge does not rule out significant neutrophilic airway inflammation. Owner satisfaction with the clinical status of the horse was uninformative.

Lung regeneration research is yielding data with increasing translational value. The classical models of lung development, postnatal alveolarization, and postpneumonectomy alveolarization have contributed to a broader understanding of the cellular participants including stem-progenitor cells, cell-cell signaling pathways, and the roles of mechanical deformation and other physiologic factors that have the potential to be modulated in human and animal patients. Although recent information is available describing the lineage fate of lung fibroblasts, genetic fate mapping, and clonal studies are lacking in the study of lung regeneration and deserve further examination. In addition to increasing knowledge concerning classical alveolarization (postnatal, postpneumonectomy), there is increasing evidence for remodeling of the adult lung after partial pneumonectomy. Though limited in scope, compelling data have emerged describing restoration of lung tissue mass in the adult human and in large animal models. The basis for this long-term adaptation to pneumonectomy is poorly understood, but investigations into mechanisms of lung regeneration in older animals that have lost their capacity for rapid re-alveolarization are warranted, as there would be great translational value in modulating these mechanisms. In addition, quantitative morphometric analysis has progressed in conjunction with developments in advanced imaging, which allow for longitudinal and nonterminal evaluation of pulmonary regenerative responses in animals and humans. This review focuses on the cellular and molecular events that have been observed in animals and humans after pneumonectomy because this model is closest to classical regeneration in other mammalian systems and has revealed several new fronts of translational research that deserve consideration.

Background Despite the increasing number of geriatric horses attended by veterinarians, there is a lack of understanding of aging-related changes on the respiratory system of horses. Objective To identify aging-related changes on the respiratory function and bronchoalveolar lavage fluid (BALF) cytology of horses. Animals Fifteen healthy young adult (2–11 years) and 16 healthy aged (≥20 years) horses. Methods The respiratory system was examined by measurement of arterial blood gases (ABG), use of respiratory inductive plethysmography (RIP) for assessment of breathing pattern and ventilatory parameters, histamine bronchoprovocation, and BALF cytology. Results No significant differences were detected with regard to values obtained by ABG or bronchoprovocation of young adult and aged healthy horses. In aged horses, there were significant differences in mean ± SD of the following parameters when compared to young horses: prolonged expiratory time (Te) measured by RIP (3.9 ± 1.5 s versus 3.0 ± 0.6 s), decreased percentage of alveolar macrophages (40.6 ± 11.3% versus 53.5 ± 9.6%), and increased percentage of lymphocytes (53.4 ± 9.5% versus 43.9 ± 11.0%). No correlations between airway reactivity and ventilatory parameters, ABG, or BALF cytology were found in this asymptomatic population. Conclusions These results suggest that aging does not cause changes in the results obtained by ABG, most RIP-derived variables, and bronchoprovocation in the horse. A decreased percentage of macrophage and an increased percentage of lymphocytes in the BALF cytology may be expected in the asymptomatic geriatric horse and may be a result of aging.

Alpha-1 antitrypsin deficiency is typified by panacinar emphysema in humans. Whilst animal models of (α1A-TD) that more accurately reflect the histology and molecular pathology of α1A-TD are in development, it is timely to discuss methods to assess emphysema severity. Several methods exist to quantify emphysema from histologic sections, including linear mean intercept (Lm), equivalent diameters (D) or their statistical derivatives (D2), and more recently probability models of D2 ("severity index"). Given proper attention to lung inflation, reference volume, and random sampling, Lm determined by intersect point counting provides a robust analytical tool to quantify emphysema severity. Details of lung preparation, processing for random sampling, and batch processing of prescreened images are provided herein.

A novel potential approach for lung transplantation could be to utilize xenogeneic decellularized pig lung scaffolds that are recellularized with human lung cells. However, pig tissues express several immunogenic proteins, notably galactosylated cell surface glycoproteins resulting from alpha 1,3 galactosyltransferase (α-gal) activity, that could conceivably prevent effective use. Use of lungs from α-gal knock out (α-gal KO) pigs presents a potential alternative and thus comparative de- and recellularization of wild-type and α-gal KO pig lungs was assessed.Decellularized lungs were compared by histologic, immunohistochemical, and mass spectrometric techniques. Recellularization was assessed following compartmental inoculation of human lung bronchial epithelial cells, human lung fibroblasts, human bone marrow-derived mesenchymal stromal cells (all via airway inoculation), and human pulmonary vascular endothelial cells (CBF) (vascular inoculation).No obvious differences in histologic structure was observed but an approximate 25% difference in retention of residual proteins was determined between decellularized wild-type and α-gal KO pig lungs, including retention of α-galactosylated epitopes in acellular wild-type pig lungs. However, robust initial recellularization and subsequent growth and proliferation was observed for all cell types with no obvious differences between cells seeded into wild-type versus α-gal KO lungs.These proof of concept studies demonstrate that decellularized wild-type and α-gal KO pig lungs can be comparably decellularized and comparably support initial growth of human lung cells, despite some differences in retained proteins. α-Gal KO pig lungs are a suitable platform for further studies of xenogeneic lung regeneration.

Lung injuries that impact the alveolus, such as emphysema, pulmonary fibrosis, and acute lung injury, are costly and prevalent problems. Moreover, the extent of alveolar injury and impairment of gas exchange is strongly associated with prognosis and survival. Thus, mechanisms of repair and regeneration of the lung alveolar compartment have received mounting attention as newer approaches to the study of stem and progenitor cells in this region unfold. The role of type II alveolar epithelial as the sole source of type I (AECI) and II (AECII) alveolar epithelial cells following lung injury has been recently challenged; recently, investigators have described stemprogenitor cells that function like precursors to AECII either in vitro or in vivo, both in mice and humans. Techniques to explore selfrenewal and multipotency have been rigorously applied to these putative stem-progenitor cell populations and the data thus far is compelling. This review provides background to the study of alveolar regeneration with the aim to provide context to the recent discoveries of putative stem-progenitor cells that may contribute to this process.

Objective—To evaluate respiratory mechanical function and bronchoalveolar lavage (BAL) cytologic results in healthy alpacas. Animals—16 client-owned adult alpacas. Procedures—Measurements of pulmonary function were performed, including functional residual capacity (FRC) via helium dilution, respiratory system resistance via forced oscillatory technique (FOT), and assessment of breathing pattern by use of respiratory inductive plethysmography (RIP) in standing and sternally recumbent alpacas. Bronchoalveolar lavage was performed orotracheally during short-term anesthesia. Results—Mean ± SD measurements of respiratory function were obtained in standing alpacas for FRC (3.19 ± 0.53 L), tidal volume (0.8 ± 0.13 L), and respiratory system resistance at 1 Hz (2.70 ± 0.88 cm H2O/L/s), 2 Hz (2.98 ± 0.70 cm H2O/L/s), 3 Hz (3.14 ± 0.77 cm H2O/L/s), 5 Hz (3.45 ± 0.91 cm H2O/L/s), and 7 Hz (3.84 ± 0.93 cm H2O/L/s). Mean phase angle, as a measurement of thoracoabdominal asynchrony, was 19.59 ± 10.06°, and mean difference between nasal and plethysmographic flow measurements was 0.18 ± 0.07 L/s. Tidal volume, peak inspiratory flow, and peak expiratory flow were significantly higher in sternally recumbent alpacas than in standing alpacas. Cytologic examination of BAL fluid revealed 58.52 ± 12.36% alveolar macrophages, 30.53 ± 13.78% lymphocytes, 10.95 ± 9.29% neutrophils, 0% mast cells, and several ciliated epithelial cells. Conclusions and Clinical Relevance—Pulmonary function testing was tolerated well in nonsedated untrained alpacas. Bronchoalveolar lavage in alpacas yielded samples with adequate cellularity that had a greater abundance of neutrophils than has been reported in horses.

Mechanical stress is an important modulator of lung morphogenesis, postnatal lung development, and compensatory lung regrowth. The effect of mechanical stress on stem or progenitor cells is unclear. We examined whether proliferative responses of epithelial progenitor cells, including dually immunoreactive (CCSP and proSP-C) progenitor cells (CCSP+/SP-C+) and type II alveolar epithelial cells (ATII), are affected by physical factors found in the lung of emphysematics, including loss of elastic recoil, reduced elastin content, and alveolar destruction. Mice underwent single lung pneumonectomy (PNY) to modulate transpulmonary pressure (mechanical stress) and to stimulate lung regeneration. Control mice underwent sham thoracotomy. Plombage of different levels was employed to partially or completely abolish this mechanical stress. Responses to graded changes in transpulmonary pressure were assessed in elastin-insufficient mice (elastin +/−, ELN+/−) and elastase-treated mice with elastase-induced emphysema. Physiological regrowth, morphometry (linear mean intercept; Lmi), and the proliferative responses of CCSP+/SP-C+, Clara cells, and ATII were evaluated. Plombage following PNY significantly reduced transpulmonary pressure, regrowth, and CCSP+/SP-C+, Clara cell, and ATII proliferation following PNY. In the ELN+/− group, CCSP+/SP-C+ and ATII proliferation responses were completely abolished, although compensatory lung regrowth was not significantly altered. In contrast, in elastase-injured mice, compensatory lung regrowth was significantly reduced, and ATII but not CCSP+/SP-C+ proliferation responses were impaired. Elastase injury also reduced the baseline abundance of CCSP+/SP-C+, and CCSP+/SP-C+ were found to be displaced from the bronchioalveolar duct junction. These data suggest that qualities of the extracellular matrix including elastin content, mechanical stress, and alveolar integrity strongly influence the regenerative capacity of the lung, and the patterns of cell proliferation in the lungs of adult mice.

Bronchoalveolar lavage (BAL) is a method for the recovery of respiratory secretions that line the peripheral airways and alveoli. Overall, BAL is considered very safe and sufficiently sensitive to detect inflammation at the cytologic level. The good correlation between BAL differential cell counts and exercise-induced hypoxemia or lactic acidosis, airway obstruction, or airway responsiveness attests to the relevance of BAL cytology to the structure and function of the equine airways. Thus, an important advantage of BAL over tracheal wash cytology is that BAL cytology relates well to the clinical signs and pathophysiologic consequences of inflammatory airway disease.

Background: The objective of this study was to examine the relationship between chronic cough, pulmonary mechanical function, bronchial hyper-responsiveness, and peripheral airway inflammation in adult performance horses with nonseptic inflammatory airway disease (IAD). Hypothesis: We hypothesized that horses with a presenting complaint of cough have a higher percentage of inflammatory cells on bronchoalveolar lavage (BAL), greater airway obstruction, and airway hyper-responsiveness (AHR) than do horses without cough. Animals/Sample Population: Adult performance horses (n = 137) referred for evaluation of signs of IAD including cough or exercise intolerance (university hospital patients) and BAL samples (n = 142) taken in first opinion practice. Methods: A descriptive, retrospective cohort analysis was performed to evaluate the association between chronic cough and pulmonary mechanical function, AHR, BAL cytology, patient signalment, and comorbid features (multivariable logistic regression). Results: Cough was significantly more prevalent in horses >7 years, and best characterized by a high BAL neutrophil count (>5%) and nasal discharge. Lung function mechanics, abnormal thoracic auscultation, and exercise intolerance did not retain statistical significance in the logistical regression analysis of cough. Although AHR was not related to neutrophilic airway inflammation (BAL neutrophils >5%), it was significantly associated with BAL mast cells >2%. Conclusions and Clinical Importance: Our data support that neutrophilic airway inflammation may potentiate cough without further changing respiratory mechanical function in IAD. In contrast, mast cell release increased AHR without affecting the incidence of cough. Cough may be used as an indicator of neutrophilic airway inflammation in the presence of low-grade nonseptic respiratory disease.

The advent of pulmonary function testing in small animals has opened the door to new interpretations of old diseases. This article reviews the salient features of airway pathophysiology in dogs and cats that relate to the interpretation of newly developed airway function tests.

Objective—To validate the use of noninvasive pulmonary function testing in sedated and nonsedated llamas and establish reference range parameters of respiratory mechanical function. Animals—10 healthy adult llamas. Procedures—Pulmonary function testing in llamas included the following: measurement of functional residual capacity (FRC) via helium dilution, respiratory inductance plethysmography (RIP) to assess breathing pattern and flow limitations, esophageal-balloon pneumotachography, and a monofrequency forced oscillatory technique (FOT; 1 to 7 Hz) before and after IM administration of xylazine (0.2 mg/kg). Results—The following mean ± SD measurements of respiratory function were obtained in nonsedated llamas: FRC (5.60 ± 1.24 L), tidal volume (1.03 ± 0.3 L), dynamic compliance (0.83 ± 0.4 L/cm H2O), pulmonary resistance (RL; 1.42 ± 0.54 cm H2O/L/s), and respiratory system resistance (2.4 ± 0.9, 2.3 ± 0.7, 2.2 ± 0.6, 2.7 ± 0.7, and 2.5 ± 0.5 cm H2O/L/s at 1, 2, 3, 5, and 7 Hz, respectively) by use of FOT. Measurements of flow limitations via RIP were comparable to other species. Sedation with xylazine induced significant increases in RL and maximum change in transpulmonary pressure. Following sedation, a mean 127% increase in RL and mean 116% increase in respiratory system resistance were observed across 1 to 7 Hz. The magnitude of change in respiratory system resistance increased with decreasing impulse frequency, suggesting bronchoconstriction. Conclusions and Clinical Relevance—Noninvasive pulmonary function testing is well tolerated in untrained unsedated llamas. These techniques have clinical applications in the diagnosis and treatment of respiratory tract disease, although testing should not be performed after sedation with xylazine.

Objective: Acute respiratory distress syndrome and acute lung injury are characterized by heterogeneous flooding/collapse of lung tissue. An emerging concept for managing these diseases is to set mechanical ventilation so as to minimize the impact of disease heterogeneity on lung mechanical stress and ventilation distribution. The goal of this study was to determine whether changes in lung mechanical heterogeneity with increasing positive end-expiratory pressure in an animal model of acute lung injury could be detected from the frequency responses of resistance and elastance. Design: Prospective, experimental study. Setting: Research laboratory at a veterinary hospital. Subjects: Female sheep weighing 48 2 kg. Interventions: In five saline-lavaged sheep, we acquired whole-lung computed tomography scans, oxygenation, static elastance, and dynamic respiratory resistance and elastance at end-expiratory pressure levels of 7.5‐20 cm H2O. Measurements and Main Results: As end-expiratory pressure increased, computed tomography-determined alveolar recruitment significantly increased but was accompanied by significant alveolar overdistension at 20 cm H2O. An optimal range of endexpiratory pressures (15‐17.5 cm H2O) was identified where alveolar recruitment was significantly increased without significant overdistension. This range corresponded to the end-expiratory pressure levels that maximized oxygenation, minimized peak-topeak ventilation pressures, and minimized indexes reflective of the mechanical heterogeneity (e.g., frequency dependence of respiratory resistance and low-frequency elastance). Static elastance did not demonstrate any significant pressure dependence or reveal an optimal end-expiratory pressure level. Conclusions: We conclude that dynamic mechanics are more sensitive than static mechanics in the assessment of the functional trade-off of recruitment relative to overdistension in a sheep model of lung injury. We anticipate that monitoring of dynamic respiratory resistance and elastance ventilator settings can be used to optimize ventilator management in acute lung injury. (Crit Care Med 2007; 35:870‐878)

The mouse is the most extensively studied animal species in respiratory research, yet the technologies available to assess airway function in conscious mice are not universally accepted. We hypothesized that whole body plethysmography employing noninvasive restraint (RWBP) could be used to quantify specific airway resistance (sRaw-RWBP) and airway responsiveness in conscious mice. Methacholine responses were compared using sRaw-RWBP vs. airway resistance by the forced oscillation technique (Raw-FOT) in groups of C57, A/J, and BALB/c mice. sRaw-RWBP was also compared with sRaw derived from double chamber plethysmography (sRaw-DCP) in BALB/c. Finally, airway responsiveness following allergen challenge in BALB/c was measured using RWBP. sRaw-RWBP in C57, A/J, and BALB/c mice was 0.51 ± 0.03, 0.68 ± 0.03, and 0.63 ± 0.05 cm/s, respectively. sRaw derived from Raw-FOT and functional residual capacity (Raw*functional residual capacity) was 0.095 cm/s, approximately one-fifth of sRaw-RWBP in C57 mice. The intra- and interanimal coefficients of variations were similar between sRaw-RWBP (6.8 and 20.1%) and Raw-FOT (3.4 and 20.1%, respectively). The order of airway responsiveness employing sRaw-RWBP was AJ > BALBc > C57 and for Raw-FOT was AJ > BALB/c = C57. There was no difference between the airway responsiveness assessed by RWBP vs. DCP; however, baseline sRaw-RWBP was significantly lower than sRaw-DCP. Allergen challenge caused a progressive decrease in the provocative concentration of methacholine that increased sRaw to 175% postsaline values based on sRaw-RWBP. In conclusion, the technique of RWBP was rapid, reproducible, and easy to perform. Airway responsiveness measured using RWBP, DCP, and FOT was equivalent. Allergen responses could be followed longitudinally, which may provide greater insight into the pathogenesis of chronic airway disease.

We applied a novel head-out plethysmographic (HOP) method to study awake canine responses to external resistive loading and natural laryngeal paralysis. Measurements of inspiratory and expiratory specific airway resistance (sRaw(insp), sRaw(exp)) were obtained before and after uni- and bidirectional loading (R(add) = 5 cmH(2)O/L/s) in large-breed dogs (n = 9). Mean sRaw(insp) after inspiratory, and sRaw(exp) after expiratory loading were 31.4 and 33.3 cmH(2)Os, respectively. Bidirectional loads induced a significantly greater rise in both sRaw(insp) and sRaw(exp) (55.1 and 61.3 cmH(2)Os) compared to unidirectional loading (P0.001). Yet, type of loading did not affect flow-volume indices. The mean R(aw) of dogs was 4.81 cmH(2)O/L/s. Expiratory loading resulted in a significant 8.8% increase in functional-residual-capacity (FRC), compared to FRC(baseline) (76.7 ml/kg). Dogs (n = 5) with laryngeal paralysis demonstrated a significant increase in sR(aw) and R(aw) compared to controls without changes in FRC. In conclusion, HOP precisely characterized sR(aw) in response to external resistive loading. Hence, we could accurately quantify airway obstruction in awake dogs with laryngeal paralysis.

There has recently been considerable interest in alternative lung-protective ventilation strategies such as variable ventilation (VV). We aimed at testing VV in a large animal lung injury model and exploring the mechanism of improvement in gas exchange seen with VV.Randomized, controlled comparative ventilation study.Research laboratory at a veterinary hospital.Female sheep weighing 59.8 +/- 10.57 kg and excised calf lungs.In a sheep saline lavage model of lung injury, we applied VV, whereby tidal volume (VT) and frequency (f) varied on each breath. Sheep were randomized into one of two groups (VV, n = 7; or control, n = 6) and ventilated for 4 hrs with all mean ventilation settings matched.Gas exchange, lung mechanics, and hemodynamic measures were recorded over the 4 hrs. VV sheep showed improvement in gas exchange (i.e., oxygenation and carbon dioxide elimination) and ventilation pressures (i.e., reduced mean and peak airway pressures) but control sheep did not. VV sheep also displayed lower-lung elastance and mechanical heterogeneity in comparison with control sheep from 2 to 4 hrs of ventilation. To study the mechanism behind improvements seen with VV, we examined the time course associated with the enhanced recruitment occurring during VV in eight saline-lavaged excised calf lungs. We found that the recruitment associated with a larger VT during VV lasted over 200 secs, nearly an order of magnitude greater than the average time interval between large VT deliveries during VV.The application of VV in a large animal model of lung injury results in improved gas exchange and superior lung mechanics in comparison with CV that can be explained at least partially by the long-lasting effects of the recruitments occurring during VV.

We have advanced a commercially available ventilator (NPB840, Puritan Bennett/Tyco Healthcare, Pleasanton, CA) to deliver an Enhanced Ventilation Waveform (EVW). This EVW delivers a broadband waveform that contains discrete frequencies blended to provide a tidal breath, followed by passive exhalation. The EVW allows breath-by-breath estimates of frequency dependence of lung and total respiratory resistance (R) and elastance (E) from 0.2 to 8 Hz. We hypothesized that the EVW approach could provide continuous ventilation simultaneously with an advanced evaluation of mechanical heterogeneities under heterogeneous airway and tissue disease conditions. We applied the EVW in five sheep before and after a bronchial challenge and an oleic acid (OA) acute lung injury model. In all sheep, the EVW maintained gas exchange during and after bronchoconstriction, as well as during OA injury. Data revealed a range of disease conditions from mild to severe with heterogeneities and airway closures. Correlations were found between the arterial partial pressure of oxygen (PaO2) and the levels and frequency-dependent features of R and E that are indicative of mechanical heterogeneity and tissue disease. Lumped parameter models provided additional insight on heterogeneous airway and tissue disease. In summary, information obtained from EVW analysis can provide enhanced guidance on the efficiency of ventilator settings and on patient status during mechanical ventilation.

The authors explored the relative utility of pulmonary function tests (PFTs) and computed tomography (CT) to characterize the progression of papain induced emphysema in sheep (n = 12). PFT included plethysmography (FRC(pleth)), helium dilution (FRC(He)), and expired reserve volume (ERV). Following papain, FRC(pleth) and FRC(He) were unchanged; ERV decreased hence residual volume increased significantly (RV + 270 mL, +86%, P = .02). In contrast, FRC by CT increased in 10 of 12 sheep (+264 mL +21%, P = .008). We conclude that plethysmography was insensitive to emphysema, but the effect on ERV (i.e., trapped gas volume) and FRC by CT were very similar, and in line with the morphologic changes in this animal model.

Objective—To evaluate the use of a modified whole body plethysmograph in awake sheep. Animals—10 healthy adult sheep. Procedure—Concurrent measurements of specific airway resistance (sRaw) and pulmonary resistance (RL) were obtained using a novel noninvasive headout constant-volume plethysmograph and esophageal balloon-pneumotachography, respectively. All data were collected before and after external resistive loading with 1 and 5.6 cm H20/L/s. Functional residual capacity (FRC) was measured by helium dilution for computation of airway resistance (Raw) preloading (Raw = sRaw/FRC). Results—The sRaw and RL were closely correlated in 10 adult sheep. Additionally, sRaw and RL accurately reflected the magnitude of added resistance. The mean FRC was 52 mL/kg and used to calculate Raw. At baseline, the values for Raw were significantly correlated with sRaw and RL. Conclusions and Clinical Relevance—Precise measurements of sRaw and Raw at baseline and sRaw after external resistive loading were obtained by use of this novel noninvasive plethysmographic technology. This method should have application to veterinary patients or animals used in research in which noninvasive rapid or serial measurements of sRaw in the conscious state are required. (Am J Vet Res 2004;65:1259–1264)

The purpose of this study was to establish reference values of respiratory mechanics and diffusion capacity in awake llamas for the interpretation and diagnosis of respiratory disease in critically ill camelids. The following procedures were performed in 10 healthy adult llamas (2–9 years; 100–204 kg): Respiratory Inductive Plethysmography and Pneumotachography (RIP) for the assessment of thoraco-abdominal synchrony and airflow obstruction (Hoffman, J Appl Physiol 2001;91: 2767–75), diffusion capacity of carbon monoxide (DLCO) and functional residual capacity (FRC) via helium dilution, esophageal balloon-pneumotachography to determine pulmonary resistance (RL) and dynamic compliance (Cdyn), as well as Monofrequency Forced Oscillatory Mechanics (FOM) (Young, J Appl Physiol 1994;76:2467–72) to establish respiratory system resistance (Rrs) and reactance (Xrs) at the oscillatory frequencies of 1,2,3,5 and 7 Hz. RIP was further performed in 3 camelid patients to determine the cause of respiratory failure. The results of conventional lung mechanics, FOM (1 Hz), DLCO and FRC in healthy llamas are listed in the table below. Rrs at 1 Hz (closest to breathing frequency) was positively correlated with RL (P=.05). The calculated mean resonant frequency was 3.37 (+/−0.68) Hz. RIP results showed a peak difference between plethysmographic flow (V'sum) and nasal flow (V'n) of 2.61 (+/−1.02) during expiration (PEsf), and 2.48 (+/−1.04) during inspiration (PIsf). The area difference between V'sum and V'n was 0.05 (+/−0.14) and 0.05 (+/−.04) during the first 25% of expiration (SFEx) and inspiration (SFIx), respectively. Noninvasive evaluation of respiratory mechanics in clinical patients was essential to establish severity, type and progression of respiratory disease, especially in camelids presenting for upper airway obstruction, pulmonary disease or thoraco-abdominal asynchrony. TV [L] PIF [L/s] PEF [L/s] FRC/ kg [ml/kg] DLCO [ml/min/ mmHg] Cdyn [L/ cmH2O] RL [cmH2O/ L/s] Rrs(1 Hz) [cmH2O/ L/s] Xrs(1 Hz) [cmH2O/ L/s] Mean 0.98 2.13 2.00 39.18 10.70 1.44 1.48 2.40 −1.17 SD 0.28 0.61 0.75 11.45 3.37 0.75 0.57 0.93 0.46

This study was conducted to determine whether horses with naturally occurring, severe chronic recurrent airway obstruction (RAO) 1) have a greater resting energy expenditure (REE) than control horses, 2) suffer body mass depletion, and 3) have significantly decreased REE after bronchodilation and, therefore, also 4) whether increased work of breathing contributes to the cachexia seen in some horses with RAO. Six RAO horses and six control horses underwent indirect calorimetric measures of REE and pulmonary function testing using the esophageal balloon-pneumotachograph method before and after treatment with ipratropium bromide, a parasympatholytic bronchodilator agent, at 4-h intervals for a 24-h period. Body condition scoring was performed, and an estimate of fat mass was determined via B-mode ultrasonography. O2 and CO2 fractions, respiratory airflow, respiratory rate, and pleural pressure changes were recorded, and O2 consumption, CO2 production, REE, pulmonary resistance, dynamic elastance, and tidal volume were calculated. In addition, we performed lung function testing and calorimetry both before and after sedation in two control horses. RAO horses had significantly lower body condition scores (2.8 ± 1.0 vs. 6.4 ± 1.2) and significantly greater O2 consumption than controls (4.93 ± 1.30 vs. 2.93 ± 0.70 ml·kg−1·min−1). After bronchodilation, there was no significant difference in O2 consumption between RAO horses and controls, although there remained evidence of residual airway obstruction. There was a strong correlation between O2 consumption and indexes of airway obstruction. Xylazine sedation was not associated with changes in pulmonary function but did result in markedly decreased REE in controls.

We have previously described the use of bronchoscopic lung volume reduction (BLVR), a novel, tissue engineering-based, minimally invasive technique, in experimental homogeneous pulmonary emphysema in sheep. In this report, we describe the use of CTguided, site-directed BLVR in the treatment of experimental heterogeneous emphysema. Nine sheep were treated with localized papain instillations and nebulized papain to generate heterogeneous emphysema. Six animals subsequently underwent BLVR while the remaining 3 served as controls. The procedure was safe and well tolerated. BLVR reduced gas trapping (26.7%) as measured by RV-to-TLC ratio, improved diffusing capacity, and reduced a bullous lesion seen by

It is almost universally accepted that respiratory disease can limit athletic performance. Because of significant respiratory reserve capacity, horses can often compete successfully in low-level competitions or during recreation even with considerable inflammatory changes within the lungs. However, such lung changes can reduce maximal aerobic exercise and have considerable impact on those horses competing in upper-level events or as racehorses. Clinical observations and physical examination findings related to the respiratory system often do not clearly indicate disease; therefore, ancillary tests are frequently required to adequately diagnose inflammatory airway dysfunction. This review will detail techniques that can provide useful diagnostic information regarding pulmonary function and outline suitable treatment modalities.

Bronchoscopic lung volume reduction (BLVR), a minimally invasive was based on the simple concept that collapse of target reprocedure based on tissue engineering principles, was performed in gions could be initiated using a washout solution to disrupt six sheep with papain-induced experimental emphysema (EMPH). surfactant function, and be maintained with a biocompatible Physiologic measurements, at baseline, after generation of EMPH, “tissue sealant” to prevent re-expansion. The concept was and at 3 and 9 weeks after BLVR, included lung volumes, diffusing tested using a sheep model of EMPH, in which lung zones capacity (DLCO), pressure–volume relationships for the lung and chest supplied by 5 to 7 mm airways were blocked, collapsed, and wall , pleural pressures generated during active respiratory muscle filled with a fibrin hydrogel sealant. This “mechanical” apcontraction, lung resistance and dynamic elastance. The animal proach to bronchoscopic volume reduction produced atelecmodel displayed hyperinflation (change in total lung capacity8%; tasis with subsequent scarring in 55% of the treated sites, change in residual volume 66%), reduced DLCO (21%), and ele- confirming the feasibility of BLVR. However, the procedure vated airway resistance (76%) that resembled advanced human was associated with a 15% incidence of sterile abscess formaEMPH. BLVR was well tolerated without complications, and it re- tion (10). Although physiologic benefits in successfully duced lung volumes (change in total lung capacity 16%; change treated sheep were comparable with those of a 20 to 25% in residual volume 55%) in a pattern that resulted in significant surgical volume reduction, the high failure rate, and unacimprovements in vital capacity (10%). At autopsy, well-organized, ceptably high incidence of abscess formation rendered this peripheral scars associated with tissue contraction were observed approach to BLVR unacceptable for clinical use. at 33 of the 36 (91%) treated sites. There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar Recently completed cell culture and large animal studies tissue, generated by BLVR, replaced hyperinflated lung, reduced suggest that to improve the effectiveness and safety of BLVR, overall lung volume, and improved respiratory function safely and consideration of biologic as well as mechanical responses consistently. The BLVR technology employed in this study addresses are necessary (11). Successful BLVR essentially requires a the limitations identified in our prior attempt at BLVR therapy and remodeling process whereby damaged, hyperinflated lung is appears safe and effective enough to justify a trial in humans. transformed into contracted scar by delivering reagents that alter the biologic environment at specific target sites. Al

Objective—To evaluate effects of sedation on stability of resistance of the respiratory system (RRS) and measures of resting energy expenditure (REE) by use of open-flow indirect calorimetry (IC) and treatment with aerosolized albuterol on REE in horses with recurrent airway obstruction (RAO). Animals—9 clinically normal horses and 8 horses with RAO. Procedure—In phase 1, RRS was measured by using forced oscillometry (FOT) in 5 clinically normal horses before and after sedation with xylazine. In phase 2, REE was measured in 4 clinically normal horses between 20 and 25 minutes and again 35 to 40 minutes after sedation with xylazine. In phase 3, IC was performed between 20 and 25 minutes and FOT was performed between 30 and 35 minutes after xylazine administration in 8 horses with RAO; after administration of 450 µg of albuterol, IC and FOT were repeated. Results—In phase 1, RRS values were significantly lower 5 and 10 minutes after sedation. In phase 2, diminishing sedation did not significantly affect REE. In phase 3, there was a significant decrease in mean RRS (1.15 ± 0.25 vs 0.84 ± 0.14 cm H20/L/s) and REE (30.68 ± 17.89 vs 27.46 ± 16.54 kcal/kg/d) after albuterol administration. Conclusions and Clinical Relevance—FOT and IC are useful in obtaining repeatable measurements of RRS and REE, respectively, in sedated horses. Concurrent bronchodilation and decreased REE after albuterol administration suggest that increased work of breathing as a result of airway obstruction may contribute to increased energy demands in horses with RAO. (Am J Vet Res2003;64:235–242)

Objective—To evaluate the association between airway reactivity and age, sex, body weight, and radiographic findings in cats. Animals—32 mature cats that constituted 2 age groups (17 young cats that were 1 to 2 years old and 15 old cats that were 12 to 13 years old). Procedure—Cats were placed in the chamber of a barometric whole-body plethysmograph (volume, 38 L), and box pressure was measured at baseline and after aerosol administration of increasing concentrations of carbachol. Airway reactivity was assessed by monitoring increases in enhanced pause (PENH), a unitless variable that measures bronchoconstriction as derived from dose-response curves. The endpoint chosen was the provocative concentration of carbachol that increased PENH to 300% of the baseline value (PCPENH300). Results—We did not find a correlation between PCPENH300 and sex, body weight, number of eosinophils, PENH before bronchoconstriction, respiratory frequency, tidal volume, or minute ventilation. Airway reactivity was significantly less in the old cats (mean ± SD PCPENH300, 0.578 ± 0.051%), compared with the value for the young cats (0.053 ± 0.006%). Radiographic patterns differed significantly between groups of cats; a greater proportion of old cats (12/15) had bronchointerstitial patterns, compared with the proportion of young cats (4/17). Conclusion and Clinical Relevance—These data support the notion that age exerts a strong influence on airway reactivity in adult cats, and radiographic differences suggest that structural changes in older cats may contribute to this effect. These findings have important implications for interpretation of results of airway reactivity tests in cats. (Am J Vet Res 2003;64:26–31)

Healthy ageing slowly transforms the structure, gas exchange efficiency, mechanical properties, immune functions, and stem-progenitor cells of the lung. Further, ageing alters the biological responses of the lung to injury, infection, and tissue resection. Regeneration of the lung can be reactivated by partial pneumonectomy (PNX), thus making PNX a unique and powerful model for the analysis of age-dependent regenerative mechanisms in the healthy lung. Specifically, the response to PNX manifests as compensatory growth and remarkable hyperplasia of stem-progenitor cells in the lung parenchyma and the formation of new alveoli by secondary septation akin to late development. Importantly, the abundance and proliferation potential of specific stem-progenitor cells in the PNX model are strikingly age dependent. This chapter focuses on important mechanisms of lung regeneration revealed by PNX that are thought to be vulnerable to healthy ageing and places those mechanisms in the context of chronic lung disease.

Respiratory inductance plethysmographic (RIP) and pneumotachographic (Pn) flows were compared dynamically in horses with bronchoconstriction. On a breath-by-breath basis, RIP was normalized to inspiratory volume from Pn, and peak [peak of subtracted final exhalation waveform (SFEmax)] and selected area [integral of subtracted final waveform during first 25% of exhaled volume (SFEint)] differences between RIP and Pn flows during early expiration were measured in three settings: 1) healthy horses ( n = 8) undergoing histamine bronchoprovocation; 2) horses with naturally occurring lower airway obstruction (AO) ( n = 7); and 3) healthy horses ( n = 6) given lobeline · HCl to induce hyperpnea. In setting 1, histamine challenge induced a dose-dependent increase in SFEmax and SFEintdifferences. A test index of airway reactivity (interpolated histamine dose that increased SFEmax by 35%) closely correlated ( r s = 0.93, P = 0.001) with a conventional index (histamine dose that induced a 35% decrease in dynamic compliance). In setting 2, in horses with AO, SFEmax and SFEint were markedly elevated, and their absolute values correlated significantly ( P < 0.005) with pulmonary resistance and the maximum change in transpulmonary pressure. The effects of bronchodilator treatment on the SFEmax and SFEint were also highly significant ( P < 0.0001). In setting 3, hyperpnea, but not tachypnea, caused significant ( P < 0.01) increases in SFEmax but not in SFEint. In conclusion, dynamic comparisons between RIP and Pn provide a defensible method for quantifying AO during tidal breathing, without the need for invasive instrumentation.

Lung volume reduction surgery (LVRS), the removal of damaged, hyperexpanded lung, has been shown to improve respiratory function in many patients with end-stage emphysema. We report the results of an animal study using a new transbronchoscopic alternative to LVRS in which a washout solution and fibrin-based glue are used to collapse, seal, and scar target regions of abnormal lung. Twelve sheep had static and dynamic lung functions measured at baseline. Emphysema was produced by inhaled papain (7,000 U/wk x 4 wk), resulting in a significant increase of lung volumes, compliance, and airway resistance. The animals were then divided into three treatment groups of four animals, and underwent surgical volume reduction (SVR), bronchoscopic volume reduction (BVR), or bronchoscopy alone (Sham-BVR). Response to each intervention was assessed 8 to 12 wk after treatment by measuring lung function and examining lung tissue. BVR and SVR groups responded with significant and similar decreases in TLC and residual volume (RV). Tissue examination demonstrated that BVR caused collapse of the lung with focal scarring in 11 of 20 target territories (55% success rate). Three of the 11 target zones developed sterile abscesses. Postprocedure complications were less frequent with BVR than with SVR. This pilot study suggests that lung volume reduction can be achieved in animals without surgery using a bronchoscopic approach and a novel fibrin-based glue system. BVR has the potential for simplifying volume reduction, extending indications, and reducing morbidity, mortality, and costs in humans.

Inflammatory airway disease (IAD) is very common in stabled horses. Short-acting beta agonist (SABA) drugs are often used to relieve clinical signs, although long-term exposure to these drugs may result in rebound bronchoconstriction. The purpose of this study was twofold: i) to describe the deposition of radiolabeled drugs using a novel one-nostril design mask-spacer combination with a breath-activated inhaler (BAI), and ii) to determine whether treatment for 10 d with inhaled albuterol using this device would impair the ability of albuterol to prevent bronchospasm during a histamine challenge test. The percentage of radio-aerosol deposited in the total lung was 12.39% ± 5.05%. All study horses demonstrated airway hyperresponsiveness (AHR) before enrollment in the study [mean provocative concentration eliciting 35% increase in delta flow (PC35)6 mg/mL histamine]. There was no significant difference in airway hyperresponsiveness to post-albuterol histamine challenge before or after treatment with albuterol. A 10-d treatment with placebo, however, caused a significant increase in airway hyperresponsiveness in all horses (P0.001). The results of this study show that the novel mask-spacer device was effective in delivering radiolabeled aerosolized drug to the lung and that delivery of a SABA for 10 d using this device did not result in increased airway hyperresponsiveness.La maladie inflammatoire des voies respiratoires (IAD) est très courante chez les chevaux gardés en écurie. Les médicaments agonistes bêta à courte action (SABA) sont souvent utilisés pour soulager les signes cliniques, bien qu’une exposition prolongée à ces médicaments puisse résulter en une bronchoconstriction rebond. Le but de la présente étude était double : i) décrire le dépôt de médicaments radio-marqués en utilisant un nouveau design de chambre d’inhalation pour une seule narine avec un inhalateur activé par l’haleine (BAI), et ii) déterminer si un traitement pendant 10 j avec de l’albuterol inhalé avec cet appareil compromettrait la capacité de l’albuterol à prévenir un bronchospasme durant un test défi à l’histamine. Le pourcentage d’aérosol radio-marqué déposé dans le poumon total était de 12,39 % ± 5,05 %. Tous les chevaux dans l’étude ont montré une hyperréactivité des voies respiratoires (AHR) avant l’incorporation dans l’étude [concentration moyenne induisant une augmentation de 35 % du delta flot (PC35)6 mg/mL d’histamine]. Il n’y avait pas de différence significative d’hyperréactivité des voies respiratoires au challenge à l’histamine post-albuterol avant ou après traitement avec de l’albuterol. Toutefois, un traitement pendant 10 j avec un placebo a causé une augmentation significative d’hyperréactivité des voies respiratoires chez tous les chevaux (

Use of de-cellularized cadaveric lungs as 3-dimensional scaffolds for ex vivo lung tissue generation offers a new potential therapeutic approach for clinical lung transplantation. However, it is likely that some of the available cadaveric human lungs may be from older donors or from donors with previously existing structural lung diseases such as emphysema or pulmonary fibrosis. It is not known whether these lungs will be suitable for either de-cellularization or re-cellularization. To investigate this, we assessed the effects of advanced age, representative emphysematous and fibrotic injuries, and the combination of advanced age and emphysematous injury and found significant differences both in histologic appearance and in the retention of extracellular matrix (ECM) and other proteins, as assessed by immunohistochemistry and mass spectrometry, between the different conditions. However, despite these differences, binding, retention and growth of bone marrow-derived mesenchymal stromal cells (MSCs) over a 1-month period following intratracheal inoculation were similar between the different experimental conditions. In contrast, significant differences occurred in the growth of C10 mouse lung epithelial cells between the different conditions. Therefore, age, lung injury, and the cell type used for re-cellularization may significantly impact the usefulness of de-cellularized whole lungs for ex vivo lung tissue regeneration.

Objective—To evaluate the effects of obesity on pulmonary function in healthy adult dogs. Animals—36 Retrievers without cardiopulmonary disease. Procedures—Dogs were assigned to 1 of 3 groups on the basis of body condition score (1 through 9): nonobese (score, 4.5 to 5.5), moderately obese (score, 6.0 to 6.5), and markedly obese (score, 7.0 to 9.0). Pulmonary function tests performed in conscious dogs included spirometry and measurement of inspiratory and expiratory airway resistance (Raw) and specific Raw (sRaw) during normal breathing and during hyperpnea via head-out whole-body plethysmography. Functional residual capacity (FRC; measured by use of helium dilution), diffusion capacity of lungs for carbon monoxide (DLCO), and arterial blood gas variables (PaO2, PaCO2, and alveolar-arterial gradient) were assessed. Results—During normal breathing, body condition score did not influence airway function, DLCO, or arterial blood gas variables. During hyperpnea, expiratory sRaw was significantly greater in markedly obese dogs than nonobese dogs and Raw was significantly greater in markedly obese dogs, compared with nonobese and moderately obese dogs. Although not significantly different, markedly obese dogs had a somewhat lower FRC, compared with other dogs. Conclusions and Clinical Relevance—In dogs, obesity appeared to cause airflow limitation during the expiratory phase of breathing, but this was only evident during hyperpnea. This suggests that flow limitation is dynamic and likely occurs in the distal (rather than proximal) portions of the airways. Further studies are warranted to localize the flow-limited segment and understand whether obesity is linked to exercise intolerance via airway dys-function in dogs.

Background: The development of bronchoscopic therapies for emphysema has renewed interest in collateral ventilation. The success or failure of bronchoscopically placed valves or biologic glues may be determined by collateral ventilation, which is exaggerated in emphysema. Furthermore, the validity of various animal models of emphysema for testing such techniques must be understood in the context of their species-specific collateral ventilation. Objectives: To quantify collateral ventilation in a sheep model of emphysema using a simple in vivo bronchoscopic method. Methods: Collateral ventilation was measured in 8 anesthetized sheep using a simple method which measured pressure and flow through the working channel of a bronchoscope wedged in a segmental lung orifice. Animals then underwent nebulized papain treatments to generate emphysema, followed by repeat bronchoscopic measurements. Results: There was a 33% decrease in resistance to collateral ventilation following papain treatment. Changes in collateral resistance were closely correlated with disease severity as measured by changes in segmental compliance, which increased 267%. Conclusions: Collateral ventilation is significantly increased in sheep following nebulized papain. Bronchoscopic measurement of collateral ventilation may be useful for evaluating other animal models of emphysema and for predicting the response to bronchoscopic therapies in human emphysema patients.

A young Golden Retriever dog developed severe respiratory distress following an initial clinical diagnosis of infectious tracheobronchitis. Severe expiratory flow limitation, associated with exertional respiratory distress and hypoxemia was present. Thoracic images obtained with conventional radiography were characterized by hyperinflation and abnormal bronchial and alveolar patterns. Computed tomography was performed and in conjunction with pulmonary functional changes was diagnostic of small airway disease. The dog was treated with a variety of antibiotics, anti-inflammatory agents, and antitussives, but the clinical signs worsened and the puppy was euthanized. Pathologic examination confirmed severe small airway disease, with emphysema and bronchiolitis.

A 5-year-old neutered male mixed breed dog presented for increased respiratory effort after being stung by over 100 bees and developing anaphylactic shock. Given the history, clinical signs and thoracic radiographic findings of a mild bilateral interstitial pattern, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) was suspected. Further testing was performed to support this diagnosis. On computed tomographic images, there was a diffuse bilateral opacification of the lungs, with preservation of bronchial and vascular margins. Pulmonary function testing indicated decreased pulmonary compliance, decreased diffusion capacity and decreased functional residual capacity. These results supported the diagnosis of ALI/ARDS secondary to bee sting envenomation and development of anaphylactic shock. After 8 days of treatment with oxygen, steroids, antibiotics, and bronchodilators the dog improved. This case demonstrates the usefulness of computed tomography and pulmonary function testing in the diagnosis of ALI/ARDS.

Background: Bronchoscopic methods for achieving lung volume reduction (BLVR) are presently undergoing clinical trials, and will soon be clinically available. Understanding the differential effects of surgical volume reduction therapy (LVRS) and BLVR on lung and chest wall physiology will assist physicians in selecting an optimal approach for patients. Objectives: Determine whether LVRS adversely affects lung or chest wall physiology at 3-month follow-up relative to BLVR in an experimental model of sheep emphysema. Methods: Twelve mixed-breed sheep were treated with papain to produce experimental emphysema, and were divided into control, LVRS, and BLVR treatment groups. Lung and chest wall impedance was measured at 0, 5, and 10 cm H2O positive end-expiratory pressure at baseline and 3-month follow-up. Results: Emphysema was associated with increased airway resistance, decreased lung tissue resistance and elastance, and increased chest wall tissue resistance. Following treatment, equivalent increases in lung elastance occurred in the LVRS and BLVR groups compared to controls. LVRS did not adversely affect chest wall impedance despite causing extensive pleural scarring. Conclusions: (1) Experimental emphysema following prolonged papain exposure progresses after cessation of treatment. (2) BLVR and LVRS produced equivalent lung and chest wall impedance responses at 3-month follow-up. (3) LVRS did not adversely affect chest wall impedance despite being associated with extensive pleural scarring.

Respiratory disease is common in captive and wild cetaceans. Bronchoscopy may permit early diagnosis of respiratory disease in dolphins and porpoises. Refinement of cetacean bronchoscopy requires development of a nomenclature system to facilitate description of the anatomic site at which lesions occur. A standard bronchoscopic nomenclature also permits serial evaluations of lesions and enhances communication between veterinarians. In this project, we adapted the bronchoscopic nomenclature devised by Amis and McKiernan for the dog and horse to the harbor porpoise (Phocoena phocoena). Silastic and air-dried models of the bronchial tree of the harbor porpoise were made to illustrate the anatomy and devise the nomenclature. Bronchial anatomy was consistent among the four porpoise lungs studied. The Amis and McKiernan nomenclature was readily adaptable to the harbor porpoise lung with minor modifications and may be useful for cetacean bronchoscopy.

Respiratory inductive plethysmography (RIP) can be used to obtain a valid measure of tidal volume in humans. This device also compares the contributions to ventilation of the thorax and abdomen. Although thoracoabdominal asynchrony is a prominent clinical feature for patients with airway obstruction, the accuracy of the RIP device to assess the severity of obstruction is unclear. This study analyzes how well RIP variables reflect the degree of a fixed external inspiratory plus expiratory resistive load in foals. Foals were employed because the species and age group are commonly afflicted with respiratory disease. Eight conscious, sedated (xylazine 1.25 mg/kg body wt) foals were subjected to randomly ordered resistive loads at the airway opening and, on a separate day, to histamine aerosol challenge. During resistive loading, phase angle changed significantly, as did phase relation ( P ≤ 0.05). However, no significant correlation was found between the degree of change in resistive load and the degree to which phase angle or relation was altered ( r s = 0.41 and 0.25, respectively). In addition, neither phase angle nor relation changed significantly with histamine challenge. We conclude that, although RIP variables changed markedly with fixed upper airway resistive loading, the degree to which they changed was erratic and therefore not useful for grading these obstructions. Furthermore, RIP variables were insensitive measures of histamine-induced bronchoconstriction.

Pulmonary function testing (PFT) may be used to help provide objective information concerning the respiratory system in dogs and cats. Available techniques for PFT include spirometry, tidal breathing flow-volume loop analysis, barometric whole-body plethysmography, dynamic and static compliance, and lung and upper airway resistance. The information gained from PFT may help both in patient management and also in gaining understanding of the pathophysiology of the pulmonary system.

The advantages of aerosol medications include the direct, topical application to the target organ (airways); rapid effect; and low systemic availability. There are now more efficient methods for aerosol delivery that facilitate the use of increasingly sophisticated aerosol drugs. This article reviews the principles of aerosol deposition and the pharmacology of current medications.