Conservative oxygen supplementation during helmet continuous positive airway pressure therapy in patients with COVID-19 and respiratory failure: a pilot study.

Background: Respiratory failure is a severe complication in coronavirus disease 2019 (COVID-19) pneumonia that, in addition to oxygen therapy, may require continuous positive airway pressure (CPAP) support. It has been postulated that COVID-19 lung injury may share some features with those observed in hyperoxic acute lung injury. Thus, a correct target arterial oxygen tension (P aO2 ) during oxygen supplementation may be crucial to protect the lung from further tissue damage. The aims of this study were: 1) to evaluate the effects of conservative oxygen supplementation during helmet CPAP therapy on mortality and intensive care unit (ICU) admission in patients with COVID-19 and respiratory failure, and 2) to evaluate the effect of conservative oxygen supplementation on new-onset organ failure and secondary pulmonary infections. Methods: This was a single-centre, historically controlled study of patients with severe respiratory failure due to COVID-19 pneumonia, receiving either conservative or nonconservative oxygen supplementation during helmet CPAP. A cohort receiving conservative oxygen supplementation was studied prospectively in which oxygen supplementation was administered with a target P aO2 <100 mmHg. Results of this cohort were compared with those of a cohort who had received liberal oxygen supplementation. Results: 71 patients were included in the conservative cohort and 75 in the nonconservative cohort. Mortality rate was lower in the conservative cohort (22.5% versus 62.7%; p<0.001). Rates of ICU admission and new-onset organ failure were lower in the conservative cohort (14.1% versus 37.3%; p=0.001 and 9.9% versus 45.3%; p<0.001, respectively). Conclusions: In patients with COVID-19 and severe respiratory failure, conservative oxygen supplementation during helmet CPAP was associated with improved survival, lower ICU admission rate and less new-onset organ failure.

High-Flow Nasal Oxygen Therapy in Acute Hypoxemic Respiratory Failure: Concise Review on Technology and Initial Methodology.

High-flow nasal cannula oxygen therapy (HFNCOT) system consists of an air/oxygen supply system capable of delivering up to 100% humidified and heated oxygen at a flow rate of up to 80 L/min. The system includes a blender, active humidifier, single heated tube, and nasal cannula. HFNCOT has many physiological advantages compared with other standard oxygen therapies, such as anatomical dead space washout, more constant fraction of inspired oxygen, positive end-expiratory (PEEP) effect, supplement of adequate humidification and maintenance of muco-ciliary function. HFNCOT is mostly used for hypoxemic acute respiratory failure, although it also has other indications. HFNCOT is a common choice of physicians as its technology makes it more silent and comfortable. Though HFNCOT is used in many clinical settings, there is a lack of publications addressing devices and initial settings. We present a review on HFNCOT, with focus on device and application methodology.

Noninvasive ventilation: education and training. A narrative analysis and an international consensus document.

Noninvasive ventilation (NIV) is an increasingly used method of respiratory support. The use of NIV is expanding over the time and if properly applied, it can save patients' lives and improve long-term prognosis. However, both knowledge and skills of its proper use as life support are paramount. This systematic review aimed to assess the importance of NIV education and training. Literature search was conducted (MEDLINE: 1990 to June, 2018) to identify randomized controlled studies and systematic reviews with the results analyzed by a team of experts across the world through e-mail based communications. Clinical trials examining the impact of education and training in NIV as the primary objective was not found. A few studies with indirect evidence, a simulation-based training study, and narrative reviews were identified. Currently organized training in NIV is implemented only in a few developed countries. Due to a lack of high-grade experimental evidence, an international consensus on NIV education and training based on opinions from 64 experts across the twenty-one different countries of the world was formulated. Education and training have the potential to increase knowledge and skills of the clinical staff who deliver medical care using NIV. There is a genuine need to develop structured, organized NIV education and training programs, especially for the developing countries.

High intensity positive pressure ventilation and long term pulmonary function responses in severe stable COPD. A delicate and difficult balance.

Method to improve minute ventilation (MV) during spontaneous breathing (SB) in stable severe chronic obstructive pulmonary disease (COPD) have a great clinical relevant in long term outcome. In this scenario, recommendations of early use of high-Intensity non-invasive Positive pressure Ventilation (HI-NPPV) or intelligent Volume Assured Pressure (iVAP) Support in Hypercapnic COPD have been proposed by safe therapeutics options. We analyze in this letter, Ekkernkamp et al. study that described the effect of HI-NPPV compared with SB on MV in patients receiving long-term treatment. We consider that interpretation of relationships between ABG, functional parameters, and respiratory mechanics reported need clarifications. Further prospective large clinical trials identifying the best mode of ventilation according to the characteristics in severe stable COPD are necessary to balance an effective approach and response on clinical symptoms and long-term effects.

Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation.

BACKGROUND: Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. METHODS: Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO(2) and PaCO(2) and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. RESULTS: Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis-metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1 ± 9.8, 36.2 ± 8.9 and 53.3 ± 4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis-metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. CONCLUSIONS: Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.

Comorbidity, hospitalization, and mortality in COPD: results from a longitudinal study.

We evaluated comorbidity, hospitalization, and mortality in chronic obstructive pulmonary disease (COPD), with special attention to risk factors for frequent hospitalizations (more than three during the follow-up period), and prognostic factors for death. Two hundred eighty-eight consecutive COPD patients admitted to respiratory medicine wards in four hospitals for acute exacerbation were enrolled from 1999 to 2000 in a prospective longitudinal study, and followed up until December 2007. The Charlson index without age was used to quantify comorbidity. Clinical and biochemical parameters and pulmonary function data were evaluated as potential predictive factors of mortality and hospitalization. FEV(1), RV, PaO(2), and PaCO(2) were used to develop an index of respiratory functional impairment (REFI index). Hypertension was the most common comorbidity (64.2%), followed by chronic renal failure (26.3%), diabetes mellitus (25.3%), and cardiac diseases (22.1%). Main causes of hospitalization were exacerbation of COPD (41.2%) and cardiovascular disease (34.4%). Most of the 56 deaths (19.4%) were due to cardiovascular disease (67.8%). Mortality risk depended on age, current smoking, FEV(1), PaO(2), the REFI index, the presence of cor pulmonale, ischemic heart disease, and lung cancer. Number and length of hospital admissions depended on the degree of dyspnea and REFI index. The correct management of respiratory disease and the implementation of aggressive strategies to prevent or treat comorbidities are necessary for better care of COPD patients.

Mechanical ventilation in patients with end-stage idiopathic pulmonary fibrosis.

BACKGROUND: Acute respiratory failure (ARF) occurring during idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis. In this subset of individuals, mechanical ventilation (MV) may be required. OBJECTIVES: We analysed the characteristics of a group of IPF patients undergoing MV for ARF in order to give some indications on the supposed prognosis. METHODS: Hospital records of 34 consecutive patients with IPF, who underwent MV for ARF, were retrospectively examined. Demographic data, time from diagnosis, gas exchange, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ARF causes and MV failure were recorded. RESULTS: Fifteen subjects (group A) underwent invasive MV and 19 patients (group B) non-invasive ventilation (NIV). The 2 groups were different for disease severity (APACHE II score 24.2 +/- 6 vs. 19.5 +/- 5.9; p = 0.01). Both ventilatory strategies temporarily increased PaO2/FiO2 as compared with spontaneous breathing (group A: 148.5 +/- 52 vs. 99 +/- 39, p = 0.0004; group B: 134 +/- 36 vs. 89 +/- 26, p = 0.0004). NIV reduced the respiratory rate (26 +/- 7 vs. 36 +/- 9 with spontaneous breathing; p = 0.002). Duration of MV correlated with the time of evolution of IPF (r = 0.45; p = 0.018). The in-hospital mortality rate was 85% (100% for invasive MV, 74% for NIV). Four of the 5 survivors died within 6 months from hospital discharge (range 2-6 months). CONCLUSIONS: MV does not appear to have a significant impact on the survival of patients with end-stage IPF. NIV may be useful for compassionate use, providing relief from dyspnoea and avoiding aggressive approaches.

Effect of insulin on airway responsiveness in patients with type 2 diabetes mellitus: a cohort study.

BACKGROUND: The correlation between low insulin levels and a decreased sensitivity of the muscarinic receptor has been shown on induced-diabetes animal models. We designed a cohort study with the aim of evaluating the effects of insulin therapy on airway responsiveness (AR) in human patients with type 2 diabetes mellitus. METHODS: We enrolled 92 patients with type 2 diabetes who had switched from oral anti-diabetic therapy to treatment by insulin subcutaneous injection. Patients were administered the methacholine challenge test (MCT) at time 0 (pre-insulin therapy) and at intervals of 15, 30, 90, 180, and 360 days after insulin treatment. The decline of forced expiratory volume in 1 second (FEV(1))% from baseline (Delta FEV(1)) in response to inhaled methacholine (MCH) was determined to assess airway hyper-responsiveness (AHR). RESULTS: A total of 81 patients (18 women and 63 men) completed the study. Their mean age was 58 +/- 7 years and the mean duration of disease was 13.5 +/- 7.7 years. The mean decrease of FEV(1) at pre-insulin assessment was 2.96 +/- 2.6%. Compared with the pre-insulin value, a significant increase of Delta FEV(1) was observed at 15, 30, and 90 days after treatment (6.25%, CI 95% 5.4 to 7.2, p = 0.0005; 7.64%, CI 95% 6.6 to 8.1, p < 0.001; 6.45%, CI 95% 5.5 to 7.3, p = 0.0004, respectively), while after 180 and 360 days AR was similar to pre-insulin values (Delta FEV(1), 3.62%, CI 95% 2.7 to 3.5 and 3.11%, CI 95% 7.9 to 9.3, respectively). CONCLUSIONS: The finding of an increased AR in patients with type 2 diabetes during the first 3 months of insulin therapy may underline the importance of monitoring pulmonary function and respiratory symptoms in patients switching from oral anti-diabetic drugs to insulin therapy, especially in the subset of individuals with respiratory disorders.

Effect of postural variations on carbon monoxide diffusing capacity in healthy subjects and patients with chronic obstructive pulmonary disease.

BACKGROUND: The scientific literature does not supply enough information about the effects of postural changes on diffusing lung capacity for carbon monoxide (DL(CO)) in patients with chronic obstructive pulmonary disease (COPD), in particular regarding the prone position. OBJECTIVES: We evaluated posture-related changes in DL(CO) in healthy subjects and in COPD patients in order to especially assess how prone posture affects gas exchange. METHODS: In this cross-sectional study, DL(CO) was measured in 10 healthy subjects and 30 COPD patients in standing, seated, supine and prone positions. RESULTS: In healthy individuals, DL(CO) tended to improve from the upright to the supine position (21.42 +/- 2.90 and 26.07 +/- 5.11 ml/min/mm Hg, respectively); in the same group, changing the position from upright to prone also caused significant improvements in DL(CO) (absolute value, 21.42 +/- 2.90 vs. 24.80 +/- 4.39 ml/min/mm Hg, p < 0.05, or percent of predicted, 78.58 +/- 11.12 vs. 91.44 +/- 13.23, p < 0.05) and in DL(CO) proportional to alveolar volume (DL(CO)/VA; 4.52 +/- 0.57 vs. 5.66 +/- 1.48 ml/min/mm Hg/l, p < 0.05). No significant differences in DL(CO) have been observed in COPD patients from the standing to the prone position. Multivariate linear regression models showed that the posture-related changes in DL(CO), DL(CO) expressed as percent of predicted and in DL(CO)/VA are directly correlated with the transition from upright/sitting to supine/prone. CONCLUSIONS: In healthy subjects, the effect of postural changes on DL(CO) could be explained by a more homogeneous perfusion, whereas the lack of variations in COPD patients could be attributed to the increased rigidity of lung capillaries, which could represent an early sensitive marker of damage of the alveolar capillary interface in these patients.

Rational timing of combination therapy with tiotropium and formoterol in moderate and severe COPD.

AIM: To determine which timing of therapy with formoterol (FOR) and/or tiotropium (TIO) shows the greater and more continuous functional improvement during 24 h in patients with moderate to severe COPD. METHODS: In this randomised, blind, crossover study 80 patients with stable COPD (40 moderate and 40 severe) received 5 different bronchodilator 30-day treatments in a random order. Treatments (Tr) were: Tr1: TIO 18 microg once-daily (8 am); Tr2: TIO 18 microg (8 am) + FOR 12 microg (8 pm); Tr3: FOR 12 microg twice-daily (8 am and 8 pm); Tr4: TIO 18 microg (8 am) + FOR 12 microg twice-daily (8 am and 8 pm); Tr5: FOR 12 microg twice-daily (8 am and 8 pm) + TIO 18 microg (8 pm). Spirometries were performed during 24 h (13 steps) on Day1 and Day30. End-points were: gain of FEV(1) (DeltaFEV(1)) from baseline of the Day1 and Day30, AUC (Area Under Curve), Dyspnoea Index, and as-needed use of salbutamol. RESULTS: Sixty-eight patients completed all treatments. The greater and continuous daily functional improvement was showed during Tr4 and Tr5 (Day1 +135.8 mL and +119.1 mL; Day30 +160.2 mL, and +160.5 mL, respectively). Daily means of DeltaFEV(1) were significantly different between single-drug treatments and combination therapy. Dyspnoea was greater in single-drug treatments. Less use of rescue salbutamol was reported in Tr4 (0.80 puffs/die) and Tr5 (0.71 puffs/die). CONCLUSIONS: In patients with moderate to severe COPD, combination therapy with tiotropium administered in the morning (Tr4) was the most effective; in patients with prevailing night-symptoms, treatment with tiotropium in the evening (Tr5) reduced symptoms and use of salbutamol. Tr5 showed less variability of FEV(1) during the 24 h (CV=0.256). These results are relevant for opening new ways in clinical practice.

Maximal respiratory static pressures in patients with different stages of COPD severity.

BACKGROUND: In this study, we analyzed maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values in a stable COPD population compared with normal subjects. We evaluated the possible correlation between functional maximal respiratory static pressures and functional and anthropometric parameters at different stages of COPD. Furthermore, we considered the possible correlation between airway obstruction and MIP and MEP values. SUBJECT AND METHODS: 110 patients with stable COPD and 21 age-matched healthy subjects were enrolled in this study. Patients were subdivided according to GOLD guidelines: 31 mild, 39 moderate and 28 severe. RESULTS: Both MIP and MEP were lower in patients with severe airway impairment than in normal subjects. Moreover, we found a correlation between respiratory muscle function and some functional and anthropometric parameters: FEV1 (forced expiratory volume in one second), FVC (forced vital capacity), PEF (peak expiratory flow), TLC (total lung capacity) and height. MIP and MEP values were lower in patients with severe impairment than in patients with a slight reduction of FEV1. CONCLUSION: The measurement of MIP and MEP indicates the state of respiratory muscles, thus providing clinicians with a further and helpful tool in monitoring the evolution of COPD.

Herpes simplex pneumonia: Combination therapy with oral acyclovir and aerosolized ribavirin in an immunocompetent patient.

BACKGROUND: Herpes simplex viruses (HSVs) are known to cause respiratory tract infections in immunocompromised hosts and, in rare instances, in immunocompetent hosts. Numerous in vitro and in vivo studies have shown that aerosolized administration of ribavirin can potently and selectively inhibit viral replication in pulmonary disease, thereby increasing the effectiveness of acyclovir in HSV. OBJECTIVE: In this case study, we reported on a 46-year-old immunocompetent woman with HSV type 1 pneumonia with bilateral pulmonary infiltrates but without mucocutaneous lesions. METHODS: The diagnosis was confirmed using cytology, viral culture, and serology. Because of the persistence of fever and dyspnea, we chose an antiviral therapy. The patient received oral acyclovir and aerosolized ribavirin to improve the antiviral effectiveness of the acyclovir and to reduce the symptoms and the time to resolution of the pulmonary disease. RESULTS: After 3 days of therapy, dyspnea and fever decreased and hypoxemia improved. After 2 weeks, computed tomography showed complete resolution of pulmonary abnormalities. The patient did not report any adverse effects. CONCLUSIONS: In our case study, we demonstrated that therapy with a combination of aerosolized ribavirin and oral acyclovir may be useful to reduce the severity of viral infection, the adverse effects, and the days of hospitalization. To our knowledge, this is the first report in the literature of the synergistic effects of the combination of aerosolized ribavirin and oral acyclovir in the treatment of an immunocompetent patient with HSV pneumonia.