Chest physiotherapy techniques administered by certified specialists to hospitalized patients with COVID-19 in Brazil: A look towards future practice.

BACKGROUND: Chest physiotherapy for hospitalized patients with COVID-19 has been poorly reported. Although recommendations were published to guide physiotherapists, practice might have differed depending on education and training. OBJECTIVE: To analyze the differences in chest physiotherapy applied for hospitalized patients with COVID-19 between certified specialists and non-certified specialists. METHODS: An online questionnaire survey was developed for physiotherapists involved in the management of hospitalized patients with COVID-19. The questionnaire inquired about professional information and characteristics of physiotherapy practice. RESULTS: There were 485 respondents, yielding a completion rate of 76%. Of these, 61 were certified specialists and 424 non-certified specialists. The certified specialists were older, had more years of professional experience, were more qualified, and had better job conditions. For mechanically ventilated patients, the certified specialists used the ventilator hyperinflation maneuver more frequently (50.4% vs 35.1%, p = 0.005), and the hard/brief expiratory rib cage compression (ERCC) (26.9% vs 48.3%, p = 0.016), soft/long ERCC (25.2% vs 39.1%, p = 0.047), and manual chest compression-decompression (MCCD) maneuver (22.4% vs 35.6%, p = 0.001) less often. For spontaneously breathing patients, the certified specialists used the active cycle of breathing technique (30.8% vs 67.1%, p<0.001), autogenic drainage (7.7% vs 20.7%, p = 0.017), and MCCD maneuver (23.1% vs 41.4%, p = 0.018) less frequently. CONCLUSIONS: Certified specialists with higher levels of expertise seem to prefer the use of chest physiotherapy techniques that are applied with the mechanical ventilator over manual techniques. Furthermore, they use techniques that could potentially increase the work of breathing less frequently, mitigating the risk of exacerbating respiratory conditions in patients with COVID-19.

Chest physiotherapy for pneumonia in adults.

BACKGROUND: Despite conflicting evidence, chest physiotherapy has been widely used as an adjunctive treatment for adults with pneumonia. This is an update of a review first published in 2010 and updated in 2013. OBJECTIVES: To assess the effectiveness and safety of chest physiotherapy for pneumonia in adults. SEARCH METHODS: We updated our searches in the following databases to May 2022: the Cochrane Central Register of Controlled Trials (CENTRAL) via OvidSP, MEDLINE via OvidSP (from 1966), Embase via embase.com (from 1974), Physiotherapy Evidence Database (PEDro) (from 1929), CINAHL via EBSCO (from 2009), and the Chinese Biomedical Literature Database (CBM) (from 1978). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs assessing the efficacy of chest physiotherapy for treating pneumonia in adults. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two new trials in this update (540 participants), for a total of eight RCTs (974 participants). Four RCTs were conducted in the United States, two in Sweden, one in China, and one in the United Kingdom. The studies looked at five types of chest physiotherapy: conventional chest physiotherapy; osteopathic manipulative treatment (OMT, which includes paraspinal inhibition, rib raising, and myofascial release); active cycle of breathing techniques (which includes active breathing control, thoracic expansion exercises, and forced expiration techniques); positive expiratory pressure; and high-frequency chest wall oscillation. We assessed four trials as at unclear risk of bias and four trials as at high risk of bias. Conventional chest physiotherapy (versus no physiotherapy) may have little to no effect on improving mortality, but the certainty of evidence is very low (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.15 to 7.13; 2 trials, 225 participants; I² = 0%). OMT (versus placebo) may have little to no effect on improving mortality, but the certainty of evidence is very low (RR 0.43, 95% CI 0.12 to 1.50; 3 trials, 327 participants; I² = 0%). Similarly, high-frequency chest wall oscillation (versus no physiotherapy) may also have little to no effect on improving mortality, but the certainty of evidence is very low (RR 0.75, 95% CI 0.17 to 3.29; 1 trial, 286 participants). Conventional chest physiotherapy (versus no physiotherapy) may have little to no effect on improving cure rate, but the certainty of evidence is very low (RR 0.93, 95% CI 0.56 to 1.55; 2 trials, 225 participants; I² = 85%). Active cycle of breathing techniques (versus no physiotherapy) may have little to no effect on improving cure rate, but the certainty of evidence is very low (RR 0.60, 95% CI 0.29 to 1.23; 1 trial, 32 participants). OMT (versus placebo) may improve cure rate, but the certainty of evidence is very low (RR 1.59, 95% CI 1.01 to 2.51; 2 trials, 79 participants; I² = 0%). OMT (versus placebo) may have little to no effect on mean duration of hospital stay, but the certainty of evidence is very low (mean difference (MD) -1.08 days, 95% CI -2.39 to 0.23; 3 trials, 333 participants; I² = 50%). Conventional chest physiotherapy (versus no physiotherapy, MD 0.7 days, 95% CI -1.39 to 2.79; 1 trial, 54 participants) and active cycle of breathing techniques (versus no physiotherapy, MD 1.4 days, 95% CI -0.69 to 3.49; 1 trial, 32 participants) may also have little to no effect on duration of hospital stay, but the certainty of evidence is very low. Positive expiratory pressure (versus no physiotherapy) may reduce the mean duration of hospital stay by 1.4 days, but the certainty of evidence is very low (MD -1.4 days, 95% CI -2.77 to -0.03; 1 trial, 98 participants). Positive expiratory pressure (versus no physiotherapy) may reduce the duration of fever by 0.7 days, but the certainty of evidence is very low (MD -0.7 days, 95% CI -1.36 to -0.04; 1 trial, 98 participants). Conventional chest physiotherapy (versus no physiotherapy, MD 0.4 days, 95% CI -1.01 to 1.81; 1 trial, 54 participants) and OMT (versus placebo, MD 0.6 days, 95% CI -1.60 to 2.80; 1 trial, 21 participants) may have little to no effect on duration of fever, but the certainty of evidence is very low. OMT (versus placebo) may have little to no effect on the mean duration of total antibiotic therapy, but the certainty of evidence is very low (MD -1.07 days, 95% CI -2.37 to 0.23; 3 trials, 333 participants; I² = 61%). Active cycle of breathing techniques (versus no physiotherapy) may have little to no effect on duration of total antibiotic therapy, but the certainty of evidence is very low (MD 0.2 days, 95% CI -4.39 to 4.69; 1 trial, 32 participants). High-frequency chest wall oscillation plus fibrobronchoscope alveolar lavage (versus fibrobronchoscope alveolar lavage alone) may reduce the MD of intensive care unit (ICU) stay by 3.8 days (MD -3.8 days, 95% CI -5.00 to -2.60; 1 trial, 286 participants) and the MD of mechanical ventilation by three days (MD -3 days, 95% CI -3.68 to -2.32; 1 trial, 286 participants), but the certainty of evidence is very low. One trial reported transient muscle tenderness emerging after OMT in two participants. In another trial, three serious adverse events led to early withdrawal after OMT. One trial reported no adverse events after positive expiratory pressure treatment. Limitations of this review were the small sample size and unclear or high risk of bias of the included trials. AUTHORS' CONCLUSIONS: The inclusion of two new trials in this update did not change the main conclusions of the original review. The current evidence is very uncertain about the effect of chest physiotherapy on improving mortality and cure rate in adults with pneumonia. Some physiotherapies may slightly shorten hospital stays, fever duration, and ICU stays, as well as mechanical ventilation. However, all of these findings are based on very low certainty evidence and need to be further validated.

Antioxidant Biodegradable Covalent Cyclodextrin Frameworks as Particulate Carriers for Inhalation Therapy against Acute Lung Injury.

Drug therapies for acute lung injury (ALI) are far from satisfactory, primarily because drugs cannot specifically target the lungs. Direct delivery of drugs to the deep alveolar regions by inhalation administration is crucial for the treatment of ALI. However, conventional inhalable carriers such as lactose and mannitol are generally inactive. Therefore, the use of a novel pharmacologically active carrier for pulmonary delivery may produce synergetic effects in treating ALI. Considering the pathophysiological environment of ALI, which typically featured excessive reactive oxygen species (ROS) and acute inflammation, we synthesized a novel kind of biodegradable and ROS-sensitive cross-linked covalent cyclodextrin frameworks (OC-COF) with uniform inhalable particle size to treat ALI. OC-COF was devised to incorporate H2O2-scavenging peroxalate ester linkages, which could hydrolyze and eliminate ROS generated in inflammatory sites. Ligustrazine (LIG), an antioxidant and anti-inflammatory natural compound, was loaded into OC-COF and evaluated as a dry powder inhaler (LIG@OC-COF) in vitro and in vivo, showing favorable aerodynamic properties and prominent antioxidant and anti-inflammatory capacities for the synergistic effects of OC-COF and LIG. In ALI rats, inhalation of LIG@OC-COF with a one-fifth LIG dose significantly alleviated the inflammation, oxidant stress, and lung damage. Western blot analysis demonstrated that LIG@OC-COF protected the lungs by regulating the Nrf2/NF-κB signaling pathway. In summary, this study provides a novel ROS-responsive material as an inhalable particulate carrier for the improved treatment of ALI and other medical conditions.

Emergency Department Visits Due to Dyspnea: Association with Inhalation Therapy in COPD and Cases with Adverse Drug Reactions.

Purpose: Dyspnea is a leading symptom of COPD that causes presentations in emergency departments or negatively impacts on them. Guideline-based inhalation therapies are intended to reduce dyspnea in COPD patients. This study analyzed how common guideline recommended inhalation therapy regimens are occurring in clinical practice among COPD patients presenting to emergency departments due to adverse drug reactions in polytherapy using data of the German ADRED database. Patients and Methods: In total, 269 COPD cases were identified. In a further analysis, all cases were analyzed for documented GOLD stage and guideline-recommended inhalation therapy for COPD. Dyspnea and other symptoms identified during ED presentation were analyzed and compared between patients who did and did not receive the guideline's recommended inhalation therapy. Results: In this observation, 41% (n = 46) of all 112 cases with a documented COPD and GOLD stage received an underdosed therapy according to current guidelines. Dyspnea was the most common identified symptom (32%, n = 36) in this cohort and occurred more often in patients who received an underdosage of inhalation therapy (p < 0.01). Conclusion: Patients with COPD presenting to ED with ADRs show a high rate of non-guideline-recommended inhalation therapy and present more often with dyspnea compared to those COPD patients who received an adequate dosing of inhalation therapy.

Aerosol release, distribution, and prevention during aerosol therapy: a simulated model for infection control.

Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory conditions. A potential consequence of this form of treatment is the release of fugitive aerosols, both patient derived and medical, into the environment and the subsequent exposure of caregivers and bystanders to potential viral infections. This study examined the release of these fugitive aerosols during a standard aerosol therapy to a simulated adult patient. An aerosol holding chamber and mouthpiece were connected to a representative head model and breathing simulator. A combination of laser and Schlieren imaging was used to non-invasively visualize the release and dispersion of fugitive aerosol particles. Time-varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions to the simulated patient. The influence of breathing pattern, normal and distressed, supplemental air flow, at 0.2 and 6 LPM, and the addition of a bacterial filter to the exhalation port of the mouthpiece were assessed. Images showed large quantities of fugitive aerosols emitted from the unfiltered mouthpiece. The images and particle counter data show that the addition of a bacterial filter limited the release of these fugitive aerosols, with the peak fugitive aerosol concentrations decreasing by 47.3-83.3%, depending on distance from the simulated patient. The addition of a bacterial filter to the mouthpiece significantly reduces the levels of fugitive aerosols emitted during a simulated aerosol therapy, p≤ .05, and would greatly aid in reducing healthcare worker and bystander exposure to potentially harmful fugitive aerosols.

Safety, tolerability and efficacy of LEGA-Kid® mechanical percussion device versus conventional chest physiotherapy in children: a randomised, single-blind controlled study.

INTRODUCTION: Chest physiotherapy (CPT) may benefit children aged below five years who suffer from lower respiratory tract infection (LRTI). However, its effects depend on the technique used. This study aimed to determine whether mechanical CPT using the LEGA-Kid® mechanical percussion device is superior to manual CPT in children with LRTI. METHODS: Children aged five months to five years who were admitted and referred for CPT from January to April 2017 were randomised to either manual CPT or mechanical CPT with LEGA-Kid. Outcomes measured before intervention and two hours after intervention were respiratory rate (RR), oxygen saturation and modified Respiratory Distress Assessment Instrument (mRDAI) score. RESULTS: All 30 enrolled patients showed significant reduction in post-intervention RR and mRDAI scores. There was an 8% reduction in RR for the manual CPT group (p = 0.002) and a 16.5% reduction in the mechanical CPT group (p = 0.0001), with a significantly greater reduction in the latter (p = 0.024). mRDAI scores decreased by 2.96 in the manual group (p = 0.0001) and 3.62 in the mechanical group (p = 0.002), with no significant difference between the groups. There was no significant improvement in oxygen saturation, and no adverse events were observed after CPT. CONCLUSION: Children receiving both manual and mechanical CPT showed improvements in respiratory distress symptoms, with no adverse effects. A combined strategy of nebulised hypertonic saline followed by CPT for LRTI removes airway secretions and results in improvements in moderately severe respiratory distress. The LEGA-Kid mechanical CPT method is superior to manual CPT in reducing the RR.

An in vitro visual study of fugitive aerosols released during aerosol therapy to an invasively ventilated simulated patient.

COVID-19 can cause serious respiratory complications resulting in the need for invasive ventilatory support and concurrent aerosol therapy. Aerosol therapy is considered a high risk procedure for the transmission of patient derived infectious aerosol droplets. Critical-care workers are considered to be at a high risk of inhaling such infectious droplets. The objective of this work was to use noninvasive optical methods to visualize the potential release of aerosol droplets during aerosol therapy in a model of an invasively ventilated adult patient. The noninvasive Schlieren imaging technique was used to visualize the movement of air and aerosol. Three different aerosol delivery devices: (i) a pressurized metered dose inhaler (pMDI), (ii) a compressed air driven jet nebulizer (JN), and (iii) a vibrating mesh nebulizer (VMN), were used to deliver an aerosolized therapeutic at two different positions: (i) on the inspiratory limb at the wye and (ii) on the patient side of the wye, between the wye and endotracheal tube, to a simulated intubated adult patient. Irrespective of position, there was a significant release of air and aerosol from the ventilator circuit during aerosol delivery with the pMDI and the compressed air driven JN. There was no such release when aerosol therapy was delivered with a closed-circuit VMN. Selection of aerosol delivery device is a major determining factor in the release of infectious patient derived bioaerosol from an invasively mechanically ventilated patient receiving aerosol therapy.

Effects of three pulmonary ventilation regimes in patients undergoing coronary artery bypass graft surgery: a randomized clinical trial.

The aim was to compare the effect of diaphragmatic breathing exercise (DBE), flow- (FIS) and volume-oriented incentive spirometry (VIS) on pulmonary function- (PFT), functional capacity-6-Minute Walk Test (6 MWT) and Functional Difficulties Questionnaire (FDQ) in subjects undergoing Coronary Artery Bypass Graft surgery (CABG). The purpose of incorporating pulmonary ventilator regimes is to improve ventilation and avoid post-operative pulmonary complications. CABG patients (n = 72) were allocated to FIS, VIS and DBE groups (n = 24 each) by block randomization. Preoperative and postoperative values for PFT were taken until day 7 for all three groups. On 7th postoperative day, 6 MWT and FDQ was analyzed using ANOVA and post-hoc analysis. PFT values were found to be decreased on postoperative day 1(Forced Vital Capacity (FVC) = FIS group-65%, VIS group-47%, DBE group-68%) compared to preoperative day (p < 0.001). PFT values for all 3 groups recovered until postoperative day 7 (FVC = FIS group-67%, VIS group-95%, DBE group-59%) but was found to reach the baseline in VIS group (p < 0.001). When compared between 3 groups, statistically significant improvement was observed in VIS group (p < 0.001) in 6 MWT and FDQ assessment. In conclusion, VIS was proven to be more beneficial in improving the pulmonary function (FVC), functional capacity and FDQ when compared to FIS and DBE.

A Flexible Enclosure to Protect Respiratory Therapists During Aerosol-Generating Procedures.

BACKGROUND: Exposure of respiratory therapists (RTs) during aerosol-generating procedures such as endotracheal intubation is an occupational hazard. Depending on the hospital, RTs may serve as laryngoscopist or in a role providing ventilation support and initiating mechanical ventilation. This study aimed to evaluate the potential exposure of RTs serving in either of these roles. METHODS: We set up a simulated patient with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in an ICU setting requiring endotracheal intubation involving a laryngoscopist, a nurse, and an RT supporting the laryngoscopist. All participants wore appropriate personal protective equipment (PPE). A fluorescent marker was sprayed by an atomizer during the procedure using 3 different methods for endotracheal intubation. The 3 techniques included PPE alone, a polycarbonate intubating box, or a coronavirus flexible enclosure, which consisted of a Mayo stand with plastic covering. The laryngoscopist and the supporting RT were assessed with a black light for contamination with the fluorescent marker. All simulations were recorded. RESULTS: When using only PPE, both the laryngoscopist and the RT were grossly contaminated. When using the intubating box, the laryngoscopist's contamination was detectable only on the gloves: the gown and face shield remained uncontaminated; the RT was still grossly contaminated on the gloves, gown, neck, and face shield. When using the coronavirus flexible enclosure system, both the laryngoscopist and the RT were better protected, with contamination detected only on the gloves of the laryngoscopist and the RT. CONCLUSIONS: Of the 3 techniques, the coronavirus flexible enclosure contained the fluorescent marker more effectively during endotracheal intubation than PPE alone or the intubating box based on exposure of the laryngoscopist and supporting RT. Optimizing containment during aerosol-generating procedures like endotracheal intubation is a critical component of minimizing occupational and nosocomial spread of SARS-CoV-2 to RTs who may serve as either the laryngoscopist or a support role.

Non-invasive respiratory support for the management of transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn (TTN) is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of life in term and late preterm newborns. Supportive management might be sufficient. Non-invasive (i.e. without endotracheal intubation) respiratory support may, however, be administered to reduce respiratory distress during TTN. In addition, non-invasive respiratory support might improve clearance of lung liquid thus reducing the effort required to breathe, improving respiratory distress and potentially reducing the duration of tachypnea. OBJECTIVES: To assess benefits and harms of non-invasive respiratory support for the management of transient tachypnea of the newborn. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2), MEDLINE (1996 to 19 February 2019), Embase (1980 to 19 February 2019) and CINAHL (1982 to 19 February 2019). We applied no language restrictions. We searched clinical trial registries for ongoing studies. SELECTION CRITERIA: Randomized controlled trials, quasi-randomized controlled trials and cluster trials on non-invasive respiratory support provided to infants born at 34 weeks' gestational age or more and less than three days of age with transient tachypnea of the newborn. DATA COLLECTION AND ANALYSIS: For each of the included trials, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy, need for continuous positive airway pressure [CPAP] and need for mechanical ventilation, duration of mechanical ventilation, etc.) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcomes considered in this review were need for mechanical ventilation and pneumothorax. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included three trials (150 infants) comparing either CPAP to free-flow oxygen, nasal intermittent mandatory ventilation to nasal CPAP, or nasal high-frequency percussive ventilation versus nasal CPAP. Due to these different comparisons and to high clinical heterogeneity in the baseline clinical characteristics, we did not pool the three studies. The use of CPAP versus free oxygen did not improve the primary outcomes of this review: need for mechanical ventilation (risk ratio [RR] 0.30, 95% confidence interval [CI] 0.01 to 6.99; 1 study, 64 participants); and pneumothorax (not estimable, no cases occurred). Among secondary outcomes, CPAP reduced the duration of tachypnea as compared to free oxygen (mean difference [MD] -21.10 hours, 95% CI -22.92 to -19.28; 1 study, 64 participants). Nasal intermittent ventilation did not reduce the need for mechanical ventilation as compared with CPAP (RR 4.00, 95% CI 0.49 to 32.72; 1 study, 40 participants) or the incidence of pneumothorax (RR 1.00, 95% CI 0.07 to 14.90; 1 study, 40 participants); duration of tachypnea did not differ (MD 4.30, 95% CI -19.14 to 27.74; 1 study, 40 participants). In the study comparing nasal high-frequency ventilation to CPAP, no cases of mechanical ventilation of pneumothorax occurred (not estimable; 1 study, 46 participants); duration of tachypnea was reduced in the nasal high-frequency ventilation group (MD -4.53, 95% CI -5.64 to -3.42; 1 study, 46 participants). The quality of the evidence was very low due to the imprecision of the estimates and unclear risk of bias for detection bias and high risk of bias for reporting bias. Tests for heterogeneity were not applicable for any of the analyses as no studies were pooled. Two trials are ongoing. AUTHORS' CONCLUSIONS: There is insufficient evidence to establish the benefit and harms of non-invasive respiratory support in the management of transient tachypnea of the newborn. Though two of the included trials showed a shorter duration of tachypnea, clinically relevant outcomes did not differ amongst the groups. Given the limited and low quality of the evidence available, it was impossible to determine whether non-invasive respiratory support was safe or effective for the treatment of transient tachypnea of the newborn.

Oxidative and inflammatory effects of pulmonary rehabilitation in patients with bronchiectasis. A prospective, randomized study.

INTRODUCTION: Background: systemic inflammation and oxidative stress are important factors in the pathogenesis of bronchiectasis. Pulmonary rehabilitation (PR) is recommended for bronchiectasis, but there is no data about its effect on the inflammatory and REDOX status of these patients. Aims: to investigate the effect of PR in non-cystic-fibrosis bronchiectasis (NCFB) patients, and to compare it with the effect of PR plus a hyperproteic oral nutritional supplement (PRS) enriched with beta-hydroxy-beta-methylbutyrate (HMB) on serum inflammatory and oxidative biomarkers. Materials and methods: this was an open randomized, controlled trial. Thirty individuals (65 years old or younger with a body mass index over 18.5, older than 65 years with a body mass index over 20) were recruited from September 2013 to September 2014, and randomly assigned to receive PR or PRS. Total neutrophils, and inflammatory and oxidative biomarker levels were measured at baseline, and then at 3 and 6 months. Results: in the PRS group neutrophil levels were decreased from baseline at 6 months. A significantly different fold change was found between the PR and PRS groups. In the PR group, IL-6 and adiponectin were increased by the end of the study while TNFα levels were decreased from baseline at 6 months. REDOX biomarkers remained stable throughout the study except for 8-isoprostane levels, which were increased from baseline at 6 months in both groups of patients. Conclusions: a PR program induced a pro-oxidative effect accompanied by changes in circulating inflammatory cytokine levels in NCFB patients. Our results would also suggest a possible beneficial effect of the HMB enriched supplement on neutrophil level regulation in these patients. The information provided in this study could be useful for choosing the right therapeutic approach in the management of bronchiectasis.

INTRODUCCIÓN: Introducción: la inflamación sistémica y el estrés oxidativo son factores importantes en la patogénesis de la bronquiectasia. La rehabilitación pulmonar (PR) está recomendada en los sujetos con bronquiectasias, pero no hay datos sobre sus posibles efectos sobre el estado inflamatorio y REDOX de estos pacientes. Objetivos: investigar el efecto de la PR en pacientes con bronquiectasias no asociadas a fibrosis quística (NCFB) sobre los biomarcadores oxidativos e inflamatorios, y compararlo con los efectos de la PR junto con la suplementación oral de un suplemento hiperproteico (PRS) enriquecido con beta-hidroxi-beta-metilbutirato (HMB). Material y métodos: ensayo clínico abierto, aleatorizado y controlado. Treinta pacientes (de 65 años o menos con un índice de masa corporal por encima de 18,5, y mayores de 65 años con un índice de masa corporal de más de 20) se aleatorizaron para recibir PR o PRS. Los niveles circulantes de neutrófilos totales y los de biomarcadores de estado inflamatorio y oxidativo se determinaron al inicio del estudio y a los 3 y 6 meses. Resultados: los niveles de neutrófilos en el grupo de PRS se redujeron desde el inicio a los 6 meses, presentando una tasa de cambio significativamente diferente según el tratamiento. En el grupo de PR, la IL-6 y la adiponectina aumentaron al final del estudio, mientras que los niveles de TNFα disminuyeron desde el inicio a los 6 meses. Los biomarcadores de estrés oxidativo se mantuvieron estables durante todo el estudio excepto por los niveles de 8-isoprostano, que aumentaron desde el inicio a los 6 meses en ambos grupos de pacientes. Conclusión: el programa de PR indujo un efecto pro-oxidativo acompañado de cambios en los niveles de citoquinas inflamatorias circulantes en pacientes con NCFB. Nuestros resultados también sugieren un posible efecto beneficioso del suplemento nutricional sobre la regulación de los niveles de neutrófilos de estos pacientes.

The therapy of idiopathic pulmonary fibrosis: what is next?

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease, characterised by progressive scarring of the lung and associated with a high burden of disease and early death. The pathophysiological understanding, clinical diagnostics and therapy of IPF have significantly evolved in recent years. While the recent introduction of the two antifibrotic drugs pirfenidone and nintedanib led to a significant reduction in lung function decline, there is still no cure for IPF; thus, new therapeutic approaches are needed. Currently, several clinical phase I-III trials are focusing on novel therapeutic targets. Furthermore, new approaches in nonpharmacological treatments in palliative care, pulmonary rehabilitation, lung transplantation, management of comorbidities and acute exacerbations aim to improve symptom control and quality of life. Here we summarise new therapeutic attempts and potential future approaches to treat this devastating disease.

Early Life Supraphysiological Levels of Oxygen Exposure Permanently Impairs Hippocampal Mitochondrial Function.

Preterm infants requiring prolonged oxygen therapy often develop cognitive dysfunction in later life. Previously, we reported that 14-week-old young adult mice exposed to hyperoxia as newborns had spatial and learning deficits and hippocampal shrinkage. We hypothesized that the underlying mechanism was the induction of hippocampal mitochondrial dysfunction by neonatal hyperoxia. C57BL/6J mouse pups were exposed to 85% oxygen or room air from P2-P14. Hippocampal proteomic analysis was performed in young adult mice (14 weeks). Mitochondrial bioenergetics were measured in neonatal (P14) and young adult mice. We found that hyperoxia exposure reduced mitochondrial ATP-linked oxygen consumption and increased state 4 respiration linked proton leak in both neonatal and young adult mice while complex I function was decreased at P14 but increased in young adult mice. Proteomic analysis revealed that hyperoxia exposure decreased complex I NDUFB8 and NDUFB11 and complex IV 7B subunits, but increased complex III subunit 9 in young adult mice. In conclusion, neonatal hyperoxia permanently impairs hippocampal mitochondrial function and alters complex I function. These hippocampal mitochondrial changes may account for cognitive deficits seen in children and adolescents born preterm and may potentially be a contributing mechanism in other oxidative stress associated brain disorders.

Pneumonia Prevention Strategies for Children With Neurologic Impairment.

BACKGROUND: Children with neurologic impairment (NI) face high risk of recurrent severe pneumonia, with prevention strategies of unknown effectiveness. We evaluated the comparative effectiveness of secondary prevention strategies for severe pneumonia in children with NI. METHODS: We included children enrolled in California Children's Services between July 1, 2009, and June 30, 2014, with NI and 1 pneumonia hospitalization. We examined associations between subsequent pneumonia hospitalization and expert-recommended prevention strategies: dental care, oral secretion management, gastric acid suppression, gastrostomy tube placement, chest physiotherapy, outpatient antibiotics before index hospitalization, and clinic visit before or after index hospitalization. We used a 1:2 propensity score matched model to adjust for covariates, including sociodemographics, medical complexity, and severity of index hospitalization. RESULTS: Among 3632 children with NI and index pneumonia hospitalization, 1362 (37.5%) had subsequent pneumonia hospitalization. Only dental care was associated with decreased risk of subsequent pneumonia hospitalization (adjusted odds ratio [aOR]: 0.64; 95% confidence interval [CI]: 0.49-0.85). Exposures associated with increased risk included gastrostomy tube placement (aOR: 2.15; 95% CI: 1.63-2.85), chest physiotherapy (aOR: 2.03; 95% CI: 1.29-3.20), outpatient antibiotics before hospitalization (aOR: 1.42; 95% CI: 1.06-1.92), clinic visit before (aOR: 1.30; 95% CI: 1.11-1.52), and after index hospitalization (aOR: 1.72; 95% CI: 1.35-2.20). CONCLUSIONS: Dental care was associated with decreased recurrence of severe pneumonia. Several strategies, including gastrostomy tube placement, were associated with increased recurrence, possibly due to unresolved confounding by indication. Our results support a clinical trial of dental care to prevent severe pneumonia in children with NI.

Validity and Reliability of a New Tool to Evaluate Impaired Airway Clearance in Hospitalized Pediatric Subjects With Respiratory Distress.

BACKGROUND: Chest physiotherapy has been reported to be beneficial in specific clinical contexts, yet it carries a risk of potential serious adverse events with little benefit in other patients. Therefore, identifying and limiting airway clearance therapies to patients with the greatest potential benefit and least risk is clinically relevant and important. This study aims to validate the Airway Clearance and Expansion Index (ACE-I) for the serial assessment of hospitalized pediatric patients with impaired airway clearance and to establish reliability in score acquisition across a range of pediatric respiratory disease states. METHODS: Content validity of the category importance and category choices was assessed via a survey of well-established pediatric pulmonary and critical care physicians, as well as respiratory therapists (RTs). Inter-rater reliability testing was performed on hospitalized children from October 2016 through April 2017 and analyzed using a one-way random effects intraclass correlation. RESULTS: 51 providers (24 of 37 physicians and 27 of 92 RTs) responded to the survey. Agreement was defined as any score of 6 or greater out of 10 on a scale of 1-10. The total ACE-I scale content validity index (S-CVI) scores for category importance and category choices for physicians were 1 and 0.75, respectively, and for RTs the scores were 0.75 and 0.75, respectively. 172 subjects were scored by multiple raters, resulting in an excellent overall intraclass correlation coefficient of 0.77 (95% CI 0.71-0.83) and the following component scores: cough, 0.72 (95% CI 0.64-0.79); breath sounds, 0.54 (95% CI 0.43-0.64); chest radiograph findings, 0.84 (95% CI 0.79-0.88); and secretions 0.85, (95% CI 0.81-0.89). CONCLUSIONS: The ACE-I score addresses and quantifies 4 components of the respiratory assessment that RTs and pediatric physicians deem important in identifying patients who have impaired airway clearance and might benefit from airway clearance and expansion therapies. In addition, the ACE-I score had excellent inter-rater reliability and clinical feasibility within our single institution.

Chest physiotherapy for pneumonia in children.

BACKGROUND: Pneumonia is a lung infection that causes more deaths in children aged under five years than any other single cause. Chest physiotherapy is widely used as adjuvant treatment for pneumonia. Physiotherapy is thought to help remove inflammatory exudates, tracheobronchial secretions, and airway obstructions, and reduce airway resistance to improve breathing and enhance gas exchange. This is an update of a review published in 2013. OBJECTIVES: To assess the effectiveness of chest physiotherapy with regard to time until clinical resolution in children (from birth to 18 years) of either gender with any type of pneumonia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (22 February 2018), Embase (22 February 2018), CINAHL (22 February 2018), LILACS (22 February 2018), Web of Science (22 February 2018), and PEDro (22 February 2018). We also searched clinical trials registers (ClinicalTrials.gov and WHO ICTRP) to identify planned, ongoing, and unpublished trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any type of chest physiotherapy with no chest physiotherapy for children with pneumonia. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The primary outcomes of interest were mortality, duration of hospital stay, and time to clinical resolution. We used Review Manager 5 software to analyse data and GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: We included three new RCTs for this update, for a total of six included RCTs involving 559 children aged from 29 days to 12 years with pneumonia who were treated as inpatients. Pneumonia severity was described as moderate in one trial, severe in two trials, and was not stated in three trials. The studies assessed five different interventions: effects of conventional chest physiotherapy (3 studies, 211 children), positive expiratory pressure (1 study, 72 children), continuous positive airway pressure (CPAP) (1 study, 94 children), bubble CPAP (bCPAP) (1 study, 225 children), and assisted autogenic drainage (1 studies, 29 children). The included studies were conducted in Bangladesh, Brazil, China, Egypt, and South Africa. The studies were overall at low risk of bias. Blinding of participants was not possible in most studies, but we considered that the outcomes were unlikely to be influenced by the lack of blinding.All included studies evaluated mortality. However, three studies assessed mortality as an outcome, and only one study of bCPAP reported that deaths occurred. Three deaths occurred in children in the physiotherapy group (N = 79) and 20 deaths in children in the control group (N = 146) (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.08 to 0.90; 559 children; low-quality evidence). It is uncertain whether chest physiotherapy techniques (bCPAP, assisted autogenic drainage, and conventional chest physiotherapy) reduced hospital stay duration (days) (mean difference (MD) 0.10, 95% CI -0.56 to 0.76; 4 studies; low-quality evidence).There was variation among clinical parameters used to define clinical resolution. Two small studies found no difference in resolution of fever between children in the physiotherapy (conventional chest physiotherapy and assisted autogenic drainage) and control groups. Of five studies that considered peripheral oxygen saturation levels, only two reported that use of chest physiotherapy (CPAP and conventional chest physiotherapy) showed a greater improvement in peripheral oxygen saturation levels. However, it was unclear whether respiratory rate (breaths/min) improved after conventional chest physiotherapy (MD -2.25, 95% CI -5.17 to 0.68; 2 studies, 122 children; low-quality evidence). Two studies assessed adverse events (number of events), but only one study reported any events (RR 1.28, 95% CI 0.98 to 1.67; 2 studies, 254 children; low-quality evidence). AUTHORS' CONCLUSIONS: We could draw no reliable conclusions concerning the use of chest physiotherapy for children with pneumonia due to the small number of included trials with differing study characteristics and statistical presentation of data. Future studies should consider the following key points: appropriate sample size with adequate power to detect expected differences, standardisation of chest physiotherapy techniques, appropriate outcomes (such as duration of leukocytosis, and airway clearance), and adverse effects.

Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis.

Exhausted cluster of differentiation (CD)8+ T cells lose immunological activity due to mitochondrial dysfunction caused by peroxisome proliferator­activated receptor γ coactivator 1α (PGC­1α) inactivation, resulting in a poor prognosis in patients with cancer. As hydrogen gas was recently reported to activate PGC­1α, the present study investigated whether it restores exhausted CD8+ T cells to improve prognosis in patients with stage IV colorectal cancer. A total of 55 patients with histologically and clinically diagnosed stage IV colorectal carcinoma were enrolled between July 2014 and July 2017. The patients inhaled hydrogen gas for 3 h/day at their own homes and received chemotherapy at the Tamana Regional Health Medical Center (Tamana, Kumamoto, Japan). The CD8+ T cells were isolated from the peripheral blood and their phenotype was analyzed by flow cytometry. It was found that exhausted terminal programmed cell death 1 (PD­1)+ CD8+ T cells in the peripheral blood are independently associated with worse progression­free survival (PFS) and overall survival (OS). Notably, hydrogen gas decreased the abundance of exhausted terminal PD­1+ CD8+ T cells, increased that of active terminal PD­1­ CD8+ T cells, and improved PFS and OS times, suggesting that the balance between terminal PD1+ and PD1­ CD8+ T cells is critical for cancer prognosis. Therefore, a novel system for patient classification (category 1­4) was developed in the present study based on these two indices to assist in predicting the prognosis and therapeutic response. Collectively, the present results suggested that hydrogen gas reverses imbalances toward PD­1+ CD8+ T cells to provide an improved prognosis.

Chest physiotherapy with early mobilization may improve extubation outcome in critically ill patients in the intensive care units.

BACKGROUND: Extubation failure can lead to a longer intensive care unit (ICU) stay, higher mortality rate, and higher risk of requiring tracheostomy. Chest physiotherapy (CPT) can help patients in reducing the accumulation of airway secretion, preventing collapsed lung, improving lung compliance, and reducing comorbidities. Much research has investigated the correlation between CPT and respiratory system clearance. However, few studies have investigated the correlation between CPT and failed ventilator extubation. Therefore, this study aimed to investigate the use of CPT for reducing the rate of failed removal from mechanical ventilators. METHODS: This study was an intervention study with mechanical control. Subjects were divided into two groups. The control group, which received routine nursing chest care, was selected from a retrospective chart review. The intervention group was prospectively taken into the chest physiotherapy program. The chest physiotherapy treatment protocol consisted of inspiratory muscle training, manual hyperinflation, chest wall mobilization, secretion removal, cough function training, and early mobilization. RESULTS: A total of 439 subjects were enrolled in the intervention and control groups, with a mean age of 69 years. APACHE II score (P = .09) and GCS scores (P = .54) were similar between the two groups. Compared to the control group, patients in the intervention group had a significantly lower reintubation rate (8% vs 16%; P = .01). CONCLUSIONS: The results indicate that intensive chest physiotherapy could decrease extubation failure in mechanically ventilated patients in the ICU. In addition, chest physiotherapy could also significantly improve the rapid shallow breathing index score.

Effects of the use of respiratory physiotherapy in children admitted with acute viral bronchiolitis.

OBJECTIVE: To evaluate the effects of the use of respiratory physiotherapy in children admitted with acute viral bronchiolitis (AVB). METHODS: A literature review was done searching the Pubmed, LILACS, PEDro, and Scielo databases. The following key words were used: bronchiolitis, physiotherapy, techniques, physical therapy, and chest physiotherapy. Both controlled and uncontrolled clinical trials, without limits as to date, were selected. RESULTS: Fifteen articles were included and the use of different techniques of respiratory physiotherapy showed positive results in eight studies. Most (11) were controlled clinical trials, and only two had a double-blind design. Of the 14 studies with a control group, in six this group was submitted to nasopharyngeal aspiration. The most widely used techniques were manual vibration and postural drainage (eight studies), and then tapping/percussion (seven studied). The maneuvers considered as current, e.g., prolonged slow expiration, expiratory flow acceleration, and rhinopharyngeal retrograde clearance, were used in four, four, and two studies, respectively. CONCLUSIONS: The use of respiratory physiotherapy in children with AVB remains controversial. The heterogeneity of techniques evaluated in the studies limits the interpretation of efficacy, although its use was considered safe. Recent findings indicating a reduction in the length of the hospital stay remain to be confirmed.