Use of inhaled devices during a hospital exacerbation of COPD: a summary of an interdisciplinary audit held at ICS Maugeri Pavia, Italy (March-June 2019).

To date treatment protocols in Respiratory and or Internal departments across Italy for treatment of chronic obstructive pulmonary disease (COPD) patients at hospital admission with relapse due to exacerbation do not find adequate support in current guidelines. Here we describe the results of a recent clinical audit, including a systematic review of practices reported in literature and an open discussion comparing these to current real-life procedures. The process was dived into two 8-hour-audits 3 months apart in order to allow work on the field in between meeting and involved 13 participants (3 nurses, 1 physiotherapist, 2 internists and 7 pulmonologists). This document reports the opinions of the experts and their consensus, leading to a bundle of multidisciplinary statements on the use of inhaled drugs for hospitalized COPD patients. Recommendations and topics addressed include: i) monitoring and diagnosis during the first 24 h after admission; ii) treatment algorithm and options (i.e., short and long acting bronchodilators); iii) bronchodilator dosages when switching device or using spacer; iv) flow measurement systems for shifting to LABA+LAMA within 48 h; v) when nebulizers are recommended; vi) use of SMI to deliver LABA+LAMA when patient needs SABA <3 times/day independently from flow limitation; vii) use of DPI and pre-dosed MDI to deliver LABA+LAMA or TRIPLE when patient needs SABA <3 times/day, with inspiratory flow > 30 litres/min; viii) contraindication to use DPI; ix) continuation of LABA-LAMA when patient is already on therapy; x) possible LABA-LAMA dosage increase; xi) use of SABA and/or SAMA in addition to LABA+LABA; xii) use of SABA+SAMA restricted to real need; xiii) reconciliation of drugs in presence of comorbidities; xiv) check of knowledge and skills on inhalation therapy; xv) discharge bundle; xvi) use of MDI and SMI in tracheostomized patients in spontaneous and ventilated breathing.

Tracheostomy and related host-pathogen interaction are associated with airway inflammation as characterized by tracheal aspirate analysis.

In the last years an increasing number of subjects experienced respiratory failure and underwent tracheostomy. The aim of the present study was to analyze tracheal aspirates from the inflammatory point of view. Samples were collected from 38 consecutive tracheostomized patients: 13 COPD, 6 with neurologic disorders and 19 with other different causes of respiratory failure. We analyzed cells and soluble mediators related to inflammation and/or infection. We also compared results obtained in the tracheal aspirate of COPD patients with the same determination in the sputum of another group of non-tracheostomized COPD patients (n=41). Regardless of the underlying diagnosis, most of the samples were Pseudomonas aeruginosa positive and cells and soluble mediator did not differ. Treatment with steroids was associated with lower amount of total cells, neutrophils and lymphocytes, whereas treatment with antibiotics was not. Tracheal aspirate neutrophils correlated with PaCO(2) values; neutrophils and eosinophils correlated with their percentages in blood. As compared with sputa obtained from another group of culture-positive non-tracheostomized COPDs, tracheal aspirates showed similar cell count, proportions of inflammatory cells, and infection/inflammatory mediators. In conclusion tracheal aspirates presented high amounts of viable cells and soluble mediators independently to the cause of respiratory failure leading to tracheotomy and they represent suitable specimens to study infection/inflammation interactions.

Automatic detection of ineffective triggering and double triggering during mechanical ventilation.

OBJECTIVE: Imperfect patient-ventilator interaction is common during assisted ventilation, and the detection of clinically relevant mismatching requires visual monitoring of the ventilator screen. We have assessed the feasibility, sensitivity and specificity of an algorithm embedded in a ventilator system that is able to automatically detect the occurrence of ineffective triggering and double triggering in real time. DESIGN: Prospective study. SETTING: Respiratory intensive care unit. METHODS: Twenty patients undergoing pressure-support ventilation, either non-invasively (NIV, n=10) or conventionally ventilated (n=10), were studied. MEASUREMENTS: The detection of ineffective triggering and double triggering from the algorithm was compared by two operators with the "real" occurrence of the phenomena as assessed using the transdiaphragmatic pressure (Pdi). RESULTS: Seven of the 20 patients exhibited gross mismatching, while in the remaining patients patient-ventilator mismatching was artificially induced using a pressure control, with a low respiratory rate. Ineffective triggering and double triggering were identified by the operators in 507 and 19 of the 3343 analyzed breaths, respectively. False positives were significantly more frequent in the NIV group than with conventional ventilation. The algorithm had an overall sensitivity of 91% and specificity of 97%. Specificity was statistically higher in the conventional ventilated group than with NIV (99% vs. 95%, p<0.05). CONCLUSIONS: We have demonstrated the feasibility and efficacy of a new algorithm to detect the occurrence of impaired patient-ventilator interaction during mechanical ventilation in real time. This software may help the clinician in the identification of this problem, which has been shown to have important clinical consequences.

The effect of mouth leak and humidification during nasal non-invasive ventilation.

BACKGROUND: Poor mask fit and mouth leak are associated with nasal symptoms and poor sleep quality in patients receiving domiciliary non-invasive ventilation (NIV) through a nasal mask. Normal subjects receiving continuous positive airways pressure demonstrate increased nasal resistance following periods of mouth leak. This study explores the effect of mouth leak during pressure-targeted nasal NIV, and whether this results in increased nasal resistance and consequently a reduction in effective ventilatory support. METHODS: A randomised crossover study of 16 normal subjects was performed on separate days. Comparison was made of the effect of 5 min of mouth leak during daytime nasal NIV with and without heated humidification. Expired tidal volume (V(T)), nasal resistance (R(N)), and patient comfort were measured. RESULTS: Mean change (Delta) in V(T) and R(N) were significantly less following mouth leak with heated humidification compared to the without (DeltaV(T) -36+/-65 ml vs. -88+/-50 ml, p<0.001; DeltaR(N) +0.9+/-0.4 vs. +2.0+/-0.7 cm H(2)O l s(-1), p<0.001). Baseline comfort was worse without humidification (5.3+/-0.4 vs. 6.2+/-0.4, p<0.01), and only deteriorated following mouth leak without humidification. CONCLUSIONS: In normal subjects, heated humidification during nasal NIV attenuates the adverse effects of mouth leak on effective tidal volume, nasal resistance and improves overall comfort. Heated humidification should be considered as part of an approach to patients who are troubled with nasal symptoms, once leak has been minimised.

Physiological responses during a T-piece weaning trial with a deflated tube.

RATIONALE: T-piece trials and spontaneous breathing trials through the tracheostomy tube are often used as weaning techniques. They are usually performed with the cuff inflated, which may increase the inspiratory load and/or influence the tidal volume generated by the patient. We assessed diaphragmatic effort during T-piece trials with or without cuff inflation. SETTINGS: Respiratory intensive care unit METHODS: We measured breathing pattern, transdiaphragmatic pressure (Pdi), the pressure-time product of the diaphragm, per minute (PTPdi/min) and per breath (PTPdi/b), and lung mechanics (lung compliance and resistance) in 13 tracheotomized patients ready for a weaning trial. V(T) was recorded with respiratory inductive plethysmography (RIP-V(T)) or pneumotachography PT-V(T)). Patients completed two T-piece trials of 30[Symbol: see text]min each with or without the cuff inflated. RESULTS: RIP-V(T) and PT-V(T) values were similar with the cuff inflated, but PT-V(T) significantly underestimated RIP-V(T) when the cuff was deflated, and therefore the RIP-V(T) was chosen as the reference method. The RIP-V(T) was significantly greater and the Pdi and PTPdi/min significantly lower when the cuff was deflated than when it was inflated. The efficiency of the diaphragm, calculated by the ratio of PTPdi/b over RIP-V(T), was also improved, while no changes were observed in lung mechanics. CONCLUSIONS: Diaphragmatic effort is significantly lower during a T-piece trial with a deflated cuff than when the cuff is inflated, while RIP-V(T) is higher, so that the diaphragm's efficiency in generating tidal volume is also improved.

Effects of different ventilator settings on sleep and inspiratory effort in patients with neuromuscular disease.

Patients with neuromuscular disease (NMD) who require long-term ventilation normally have the ventilation set using empirical daytime parameters. We evaluated arterial blood gases (ABG), breathing pattern, respiratory muscle function, and sleep architecture during ventilation with two noninvasive Pressure Support Ventilation (nPSV) settings in nine patients with NMD. The two settings were randomly applied: the usual (US), with the nPSV setting titrated on simple clinical parameters, and the physiological (PHYS), tailored to the patient's respiratory effort. During wakefulness, nPSV significantly improved ABG and minute ventilation and reduced the diaphragmatic pressure-time product (PTPdi/breath), independently of the type of setting (PTPdi/breath spontaneous breathing 5.7 +/- 2.4, US 3.2 +/- 2, PHYS 3.6 +/- 1.6 cm H2O . seconds(-1), p < 0.001). However, during sleep, PHY nPSV resulted in a significant improvement of gas exchange, sleep efficiency (71.7% +/- 14 US vs. 80.6% +/- 8.3 PHYS, p < 0.01) and % of REM sleep (9.1% +/- 7 US vs. 17.3% +/- 5.4 PHYS, p < 0.01). This improvement was significantly correlated with the reduction in ineffective efforts. In NMD, nPSV is effective in improving daytime ABG and in unloading inspiratory muscles independently of whether it is set on the basis of the patient's comfort or the patient's respiratory mechanics. However, PHYS was associated with better sleep architecture and nighttime gas exchange.

Downmodulation of CXCL8/IL-8 receptors on neutrophils after recruitment in the airways.

BACKGROUND: CXCL8/IL-8 is the most significant chemokine for neutrophils, and CXC chemokine receptor (CXCR) 1 and 2 are its 2 receptors, which are downmodulated by CXCL8/IL-8 and endotoxin on activated neutrophils. OBJECTIVE: We sought to evaluate the expression of the CXCL8/IL-8 receptors and the activation marker CD11b on neutrophils in peripheral blood and in the site of airway inflammation. METHODS: The flow cytometric expression of CXCR1, CXCR2, and CD11b was evaluated on peripheral blood and induced sputum neutrophils in patients with nonsevere asthma with greater than 60% sputum neutrophils, in patients with chronic obstructive pulmonary disease (COPD), and in healthy control subjects. RESULTS: Asthmatic patients and patients with COPD had comparable expressions of CXCR1, CXCR2, and CD11b on peripheral blood and sputum neutrophils. Compared with control subjects, the peripheral neutrophil expression of CXCR2 was lower in patients with COPD ( P = .03) and that of CD11b was higher in asthmatic patients and patients with COPD ( P < .02 and P < .002). The expression of the CXCL8/IL-8 receptors on sputum neutrophils was markedly lower than on peripheral blood neutrophils ( P < .0001). The downmodulation of CXCL8/IL-8 receptors was also present in healthy control subjects but less than that seen in asthmatic patients. The difference between peripheral blood and sputum expression of CXCL8/IL-8 receptors correlated with serum CXCL8/IL-8 levels. In asthmatic patients the expression of CXCR1 and CXCR2 on sputum neutrophils negatively correlated with sputum neutrophils. CONCLUSION: In neutrophilic asthma the expression of CXCL8/IL-8 receptors on peripheral and sputum neutrophils is similar to COPD and negatively correlated with the inflammatory infiltrate in the airways. The downmodulation of CXCL8/IL-8 receptors detected in the airways should be taken into account for an eventual therapeutic inhibition of these receptors.

Noninvasive mechanical ventilation as a palliative treatment of acute respiratory failure in patients with end-stage solid cancer.

Noninvasive ventilation (NIV) is widely used in the treatment of acute respiratory failure (ARF), but not in patients with end-stage solid cancer in whom any form of mechanical ventilation tends to be avoided. In a prospective study, we investigated the use of NIV in 23 patients with solid malignancies receiving palliative care and who were affected by severe hypoxic or hypercapnic ARF. The most frequent causes of ARF were exacerbations of pre-existing pulmonary diseases and pneumonia. After one hour, NIV significantly improved PaO2/FiO2 (from 154+/-48 to 187+/-55) and the Borg dyspnoea score (from 5.5+/-1.2 to 2.3+/-0.3). NIV also improved pH, but only in the subset of hypercapnic patients. Thirteen of 23 (57%) patients were successfully ventilated and discharged alive, while 10/23 patients (43%) met the criteria for intubation or died after an initial trial of NIV. Only two of these patients accepted invasive ventilation. The mortality rate in this subgroup was 9/10 (90%). A higher Simplified Acute Physiology Score (SAPS II) and a lower PaO2/FiO2 on admission were associated with a lower probability of survival. Patients with ARF and end-stage solid malignancies have an overall ICU and 1-year mortality rate of 39% and 87%, respectively, but despite this, a consistent subset of patients may still be successfully treated with NIV, if the cause of ARF is reversible.

MVarallo: a new M(Like) alpha 1-antitrypsin-deficient allele.

A 73-year-old never-smoker woman with chronic bronchitis, increasing dyspnoea, and airflow limitation with a FEV1 of 49% of predicted value had low serum level of alpha-1-antitrypsin (69 mg/dL, normal range 150-350). Isoelectric focusing showed an Mlike pattern. Direct sequencing showed, in the second exon, a particular DNA alteration localized between codon 41 and codon 51: a region of 30 base pairs (bp) was completely deleted and substituted by a 22-bp sequence. The resulting loss of 8 bp yields, in the second exon, a 70-71 stop codon. This new Mlike variant was denominated MVarallo from the site where it was discovered.

Demographics and clinical outcomes of patients admitted to a respiratory intensive care unit located in a rehabilitation center.

INTRODUCTION: A recent survey of respiratory intensive care units (RICU) in Italy showed that RICUs in Italy are mainly (85%) located in acute care hospitals. Forty-seven percent of the patients are admitted from emergency departments, and only 18% are admitted from intensive care units (ICU), so the percentage of patients admitted for difficulty in weaning is low (8%). Patient demographics and admission patterns in RICUs located outside acute care hospitals have not been previously described. METHODS: We analyzed admission patterns, demographics, treatment, and outcomes of patients during the first year of operation of a 7-bed RICU located in a rehabilitation center that does not have an emergency department. RESULTS: In the 1-year study period, 96 RICU patients were admitted for acute or chronic respiratory failure. The patients' mean Simplified Acute Physiology Score II was 28.9 +/- 3.6. Sixty-five percent of the patients were transferred from the ICU, 17% from medical wards of other hospitals, 7% and 5%, respectively, from the medical and surgical wards of our hospital, and 6% came directly from home for a periodic check. Difficulty in weaning from mechanical ventilation was the main reason for admission (42%), followed by simple monitoring (37%) and need for acute ventilatory invasive or noninvasive support (21%). Thirty-one patients had COPD, 23 had acute hypoxemic respiratory failure, 30 had post-surgical complications, and 12 had neuromuscular disease. Twenty-seven of 40 patients admitted for difficulty in weaning were liberated from ventilation. Intrahospital mortality was 13%. Fifty percent of patients were discharged directly to home; those patients' mean Dependence Nursing Scale score (which measures the degree of patient independence) improved during hospital stay (decreased from 23 to 12 [p < 0.05]), whereas the remaining patients were transferred to long-term facilities or an acute care hospital. CONCLUSIONS: The admission pattern at our RICU in a rehabilitation center is quite different from that of an RICU in an acute care hospital. Most of our patients are admitted from ICU because of difficulty with weaning. This may be the consequence of the institutional philosophy of rehabilitation centers, which strive to achieve greater patient independence.

Weaning from tracheotomy in long-term mechanically ventilated patients: feasibility of a decisional flowchart and clinical outcome.

OBJECTIVE: To assess the feasibility of following a decisional flowchart to decide whether to remove tracheotomy in long-term mechanically ventilated patients. DESIGN AND SETTING: Prospective study in a respiratory intensive care unit, with beds dedicated to weaning from prolonged mechanical ventilation. PATIENTS AND PARTICIPANTS: 108 tracheotomized patients with respiratory failure of different causes (chronic obstructive pulmonary disease, postsurgical complications, recovery from hypoxemic respiratory failure, neuromuscular disorders), 36 of whom died or could not be weaned from mechanical ventilation. INTERVENTIONS: We applied a decisional flowchart based on some simple clinical and physiological parameters aimed at assessing the patient's ability to remove secretions, swallowing function, absence of psychiatric diseases, possibility of reaching spontaneous breathing, and amount of respiratory space. MEASUREMENTS AND RESULTS: Following our flowchart 56 of the remaining patients were successfully weaned from the tracheotomy cannula, with a reintubation rate at 3 months of 3%. The main reasons for not proceeding to decannulation were inability to remove secretions and severe glottic stenosis. No statistical differences were found between patients who received a surgical or percutaneous tracheotomy. CONCLUSIONS: Using a simple decisional flowchart we were able to remove tracheotomy cannula in almost 80% of the patients with spontaneous breathing autonomy without major clinical complications. Further larger prospective studies are needed to confirm this clinical approach in larger and different populations.

Changes in the practice of non-invasive ventilation in treating COPD patients over 8 years.

OBJECTIVE: We reviewed data of 208 episodes of acute respiratory failure due to chronic obstructive pulmonary disease treated by non-invasive ventilation (NIV) in our Respiratory Intensive Care Unit (RICU) from its opening in 1992 to 1999. MATERIAL AND METHODS: We assessed whether the rate of NIV success, the severity of the disease, and the associated costs changed in this period during which the staff and the equipment did not change. RESULTS: The failure rate was constant over the years (17.2% on average). The severity of the episodes of ARF, defined by pH and APACHE II at admission, worsened during the years. The statistical change point test allowed us to identify 1997 as the year of a significant change in the severity of admission pH and therefore to identify two different periods: 1992-1996 (mean pH = 7.25+/-0.07) and 1997-1999 (7.20+/-0.08; P<0.001). In this latter period the risk of failure for a patient with a pH <7.25 was threefold lower than in 1992-1996. In 1997-1999 an increasing number of episodes of ARF with a pH >7.28 were treated in the Medical Ward (20% vs 60%). This allowed a significant reduction of daily cost per patient treated with NIV (558+/-8 Euros vs 470+/-14 Euros, respectively; P<0.01). CONCLUSIONS: We conclude that, over time, experience with NIV may progressively allow more severely ill patients to be treated without changing the rate of success. The daily cost of NIV per patient can be reduced by treating less severely ill patients outside the RICU.