Acute dyspnea represents one of the most frequent symptoms leading to emergency room evaluation. Its significant prognostic value warrants a careful evaluation. The differential diagnosis of dyspnea is complex due to the lack of specificity and the loose association between its intensity and the severity of the underlying pathological condition. The initial assessment of dyspnea calls for prompt diagnostic evaluation and identification of optimal monitoring strategy and provides information useful to allocate the patient to the most appropriate setting of care. In recent years, accumulating evidence indicated that lung ultrasound, along with echocardiography, represents the first rapid and non-invasive line of assessment that accurately differentiates heart, lung or extra-pulmonary involvement in patients with dyspnea. Moreover, non-invasive respiratory support modalities such as high-flow nasal oxygen and continuous positive airway pressure have aroused major clinical interest, in light of their efficacy and practicality to treat patients with dyspnea requiring ventilatory support, without using invasive mechanical ventilation. This clinical review is focused on the pathophysiology of acute dyspnea, on its clinical presentation and evaluation, including ultrasound-based diagnostic workup, and on available non-invasive modalities of respiratory support that may be required in patients with acute dyspnea secondary or associated with respiratory failure.

Background: Chronic obstructive pulmonary disease (COPD) is characterised by airway obstruction with an increase in airway resistance (R) to airflow in the lungs. An extreme case of expiratory airway resistance is expiratory flow limitation, a common feature of severe COPD. Current analyses quantify expiratory R with linear model-based methods, which do not capture non-linearity's noted in COPD literature. This analysis utilises a simple nonlinear model to describe patient-specific nonlinear expiratory resistance dynamics typical of COPD and assesses its ability to both fit measured data and also to discriminate between severity levels of COPD. Methods: Plethysmographic data, including alveolar pressure and airway flow, was collected from n=100 subjects (40 healthy, 60 COPD) in a previous study. Healthy cohorts included Young (20-32 years) and Elderly (64-85 years) patients. COPD patients were divided into those with expiratory flow limitation (FL) and those without (NFL). Inspiratory R was treated as linear ( R 1 ,insp ). Expiratory R was modelled with two separate models for a comparison: linear with constant resistance ( R 1 ,exp ), and nonlinear time-varying resistance (R2,exp(t)) using bsplines. Results: Model fit to PQ loops show inspiration is typically linear. Linear R 1 ,exp captured expiratory dynamics in healthy cohorts (RMSE 0.3 [0.2- 0.4] cmH 2 O ), but did not capture nonlinearity in COPD patients. COPD cohorts showed PQ-loop ballooning during expiration, which was better captured by non-linear R 2 ,exp ( t ) (RMSE 1.7 [1.3-2.8] vs. 0.3[0.2-0.4] cmH2O in FL patients). Airway resistance is higher in COPD than healthy cohorts (mean R 2,exp (t) for Young (1.9 [1.6-2.8]), Elderly (2.4 [1.4-3.5]), NFL (4.9 [3.9-6.6]) and FL (13.5 [10.4-21.9]) cmH2O/L/s, with p <= 0.0001 between aggregated measures for Young and Elderly healthy subjects and NFL and FL COPD subjects). FL patients showed non-linear R 2 ,exp ( t ) dynamics during flow deceleration, differentiating them from NFL COPD patients. Conclusions: Linear model metrics describe expiration dynamics well in healthy subjects, but fail to capture nonlinear dynamics in COPD patients. Overall, the model-based method presented shows promise in detecting expiratory flow limitation, as well as describing different dynamics in healthy, COPD, and FL COPD patients. This method may thus be clinically useful in the diagnosis or monitoring of COPD patients using Plethysmography data, without the need for additional expiratory flow limitation confirmation procedures.

Large animals are increasingly used as experimental models of respiratory diseases. Precise characterization of respiratory mechanics requires dedicated equipment with specific characteristics which are difficult to find together in the same commercial device. In this work, we describe building and validation of a computer-controlled ventilator able to perform rapid airways occlusions during constant flow inflations followed by a prolonged inspiratory hold. A constant airflow is provided by a high pressure source (5 atm) connected to the breathing circuit by three proportional valves. The combined action of three 2-way valves produces the phases of the breath. During non-inspiratory breath phases, airflow is diverted to a flowmeter for precise feedback regulation of the proportional valves. A computer interface enables the user to change the breathing pattern, trigger test breaths or run predetermined breaths sequences. A respiratory system model was used to test the ability of the ventilator to correctly estimate interrupter resistance. The ventilator was able to produce a wide range of constant flows (0.1–1.6 L/s) with the selected timing. Errors in the measurement of interrupter resistance were small (1 ± 5% of the reference value). The device described reliably estimated interrupter resistance and can be useful as a measuring tool in large animal research.

Background: Sheep are increasingly used as experimental animal model for respiratory diseases, however, respiratory mechanics of sheep is still incompletely characterized. Aim: To assess the viscoelastic behavior of the respiratory system, chest wall and lung in the whole inspiratory capacity range using the technique of rapid interruption during constant flow inflation. Methods: 6 healthy sheep (30-52 kg) were anesthetized, paralyzed and mechanically ventilated at 0, 5, 10 and 15 cmH₂O end-expiratory pressure (ZEEP, PEEP5, 10 and 15) with constant tidal volume (8 ml/kg) and variable inspiratory flow (V̇_insp). Viscoelastic resistance (R_visc) and time-constant (τ_visc) were measured by interpolating the relation between inspiratory duration (Ti) and additional resistance (ΔR) at each PEEP level with the equation ΔR=R_visc(1-exp(-Ti/τ_visc)). ΔR is the slow pressure drop observed during a 5s post-inspiratory hold divided by V̇_insp, and reflects stress-relaxation. Esophageal pressure recording allowed to partition the viscoelastic properties of the respiratory system (rs) into those of chest wall (cw) and lung (L). Results: At ZEEP, PEEP5, 10 and 15, end-inspiratory volume was 44±8, 61±8, 79±7 and 92±5 % of vital capacity. R_visc,cw, τ_visc,rs, τ_visc,cw and τ_visc,L did not change with volume (P=0.95, 0.10, 0.69 and 0.20, respectively), while R_visc,L and thus R_visc,rs increased from ZEEP (5.3±2.0 and 9.9±1.7 cmH₂Os/L, respectively) to PEEP15 (17.9±6.0 and 26.1±9.3 cmH₂Os/L, P<0.01 and 0.02, respectively). Conclusions: Sheep lungs show a volume-dependent viscoelastic behavior. Quantitatively, the contribution of viscoelastic pressure is relevant, amounting to 10-15% of total inspiratory pressure at end-inflation.

Patients with Chronic Obstructive Pulmonary Disease (COPD) are typically instructed to inhale bronchodilators (BD) after a full deflation to residual volume (RV), a manoeuvre requiring coordination and effort. However, so far, no study has demonstrated superior BD efficacy when inhalation starts from RV compared to functional residual capacity (FRC). Since ventilation distribution heterogeneity rises with decreasing volume in COPD patients, we hypothesise that BD inhalation from different volumes may impact its efficacy. This study was aimed at comparing the effects of salbutamol via pressurized metered dose inhaler (pMDI) on lung function when inhaled from residual volume (RV) or functional residual capacity (FRC). Sixteen stable COPD patients were randomized to inhale salbutamol 400 µg from RV or from FRC during two different sessions. Dyspnea, spirometric and plethysmographic lung volumes, and phase III slope during the single-breath nitrogen test (SBN2) were assessed pre and post-BD. In both sessions, BD administration decreased dyspnea (P=0.025), increased FVC (P=0.013) and FEV1 (P=0.037) and reduced RV (P=0.003), FRC (P=0.016), sRaw (P=0.001) and phase III slope (P=0.039). The effect of BD on these parameters was not influenced by the starting inhalation volume (P>0.05). Our results suggest that inhaling a bronchodilator via pMDI from FRC rather than from RV does not affect its efficacy in terms of dyspnoea sensation and lung function. If confirmed, this finding may allow to simplify BD inhalation manoeuvres without negatively affecting BD benefits, potentially improving patients’ adherence.