Role of the active cycle of breathing technique combined with phonophoresis for the treatment of patients with chronic obstructive pulmonary disease (COPD): study protocol for a preliminary randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by coughing, the production of excess sputum, and dyspnea. Patients with excessively thick sputum may have frequent attacks or develop more serious disease. The guidelines recommend airway clearance for patients with excessive sputum who are hospitalized with COPD. The active cycle of breathing technique is the most common non-pharmacological airway clearance technique used by physiotherapists. However, the effectiveness of the technique is not always guaranteed. Active cycle of breathing techniques require the initial dilution of the sputum, usually by inhalation drugs, which may have limited effects. Recent studies have found that phonophoresis decreases inflammation, suggesting the potential of the combined usage of active cycle of breathing techniques and phonophoresis. Therefore, the aim of this study is to explore the effectiveness and safety of combining active cycle of breathing technique and phonophoresis in treating COPD patients. METHODS AND ANALYSIS: We propose a single-blind randomized controlled trial using 75 hospitalized patients diagnosed with COPD with excessive sputum production. The patients will be divided into three groups. The intervention group will receive active cycle of breathing techniques combined with phonophoresis. The two comparison groups will be treated with active cycle of breathing techniques and phonophoresis, respectively. The program will be implemented daily for 1 week. The primary outcomes will be changes in sputum viscosity and production, lung function, and pulse oximetry. Secondary outcomes include the assessment of COPD and anxiety, measured by the COPD Assessment Test scale and the Anxiety Inventory for Respiratory Disease, respectively; self-satisfaction; the degree of cooperation; and the length of hospital stay. All outcome measures, with the exception of sputum production and additional secondary outcomes, will be assessed at the commencement of the study and after 1 week's intervention. Analysis of variance will be used to investigate differences between the groups, and a p-value of less than 0.05 (two-tailed) will be considered statistically significant. DISCUSSION: This study introduces a combination of active cycle of breathing techniques and phonophoresis to explore the impact of these interventions on patients hospitalized with COPD. If this combined intervention is shown to be effective, it may prove to be a better treatment for patients with COPD. TRIAL REGISTRATION: The trial was registered prospectively on the Chinese Clinical Trial Registry on 24 December 2019.ClinicalTrials.gov ChiCTR1900028506 . Registered on December 2019.

Role of active cycle of breathing technique for patients with chronic obstructive pulmonary disease: A pragmatic, randomized clinical trial.

BACKGROUND: While active cycle of breathing technique for chronic obstructive pulmonary disease patients with more sputum can improve clinic outcomes, less is known about sputum viscosity and sputum production of the intervention. OBJECTIVE: The purpose of our study was to explore the effect of active cycle of breathing technique on sputum viscosity and production among patients with chronic obstructive pulmonary disease. DESIGN: This was a two-arms, parallel, randomized clinical trial. SETTING: Study enrollment, randomization and implementation were conducted in the department of respiratory medicine inpatient at the Medical Center in Changchun, China. PARTICIPANTS: Hospitalized patients due to chronic obstructive pulmonary disease who met additional eligibility criteria were randomized to active cycle of breathing technique (n = 50) or usual care group (n = 50). METHODS: Patients in the intervention group received a week-long intervention from an experienced physical therapist. Patients in the usual care group received usual care as well as information and advice in the light of their health plan from respiratory medicine. The primary outcome was the changes on sputum viscosity and production. RESULTS: Among one hundred patients who were randomized (mean [SD] age, 54.89 [12.06] years; females, 58%), ninety-six participants completed the study. No significant differences were found between two groups on the changes of sputum viscosity (t = 0.277, P = 0.782). And there were insignificant differences between groups in the average amount of sputum among 1 h (Z=-1.848, P = 0.065) and significant differences in the average amount of sputum among 24 h (Z=-2.236, P = 0.025). From admission to one week recovery, the changes in ratio of forced expiratory volume in 1 s to forced vital capacity (Z=-4.511, P<0.0001) and arterial oxygen saturation (Z=-2.997, P = 0.003) were better in active cycle breathing technique group. Total Chronic Obstructive Pulmonary Disease Assessment Test scale were similar among two groups (Z=-1.818, P = 0.069). No adverse events occurred during the study. CONCLUSION: For patients with chronic obstructive pulmonary disease, active cycle of breathing technique can significantly result in sputum production and respiratory function, especially those of Global Initiative for Chronic Obstructive Lung Disease classification level 3, but did not result in the short-term improvement of sputum viscosity, quality of life and cost effectiveness. Registration number: ChiCTR2000033068.

A porcine reproductive and respiratory syndrome virus candidate vaccine based on the synthetic attenuated virus engineering approach is attenuated and effective in protecting against homologous virus challenge.

Current porcine reproductive and respiratory syndrome virus (PRRSV) vaccines sometimes fail to provide adequate immunity to protect pigs from PRRSV-induced disease. This may be due to antigenic differences among PRRSV strains. Rapid production of attenuated farm-specific homologous vaccines is a feasible alternative to commercial vaccines. In this study, attenuation and efficacy of a codon-pair de-optimized candidate vaccine generated by synthetic attenuated virus engineering approach (SAVE5) were tested in a conventional growing pig model. Forty pigs were vaccinated intranasally or intramuscularly with SAVE5 at day 0 (D0). The remaining 28 pigs were sham-vaccinated with saline. At D42, 30 vaccinated and 19 sham-vaccinated pigs were challenged with the homologous PRRSV strain VR2385. The experiment was terminated at D54. The SAVE5 virus was effectively attenuated as evidenced by a low magnitude of SAVE5 viremia for 1-5 consecutive weeks in 35.9% (14/39) of the vaccinated pigs, lack of detectable nasal SAVE5 shedding and failure to transmit the vaccine virus from pig to pig. By D42, all vaccinated pigs with detectable SAVE5 viremia also had detectable anti-PRRSV IgG. Anti-IgG positive vaccinated pigs were protected from subsequent VR2385 challenge as evidenced by lack of VR2385 viremia and nasal shedding, significantly reduced macroscopic and microscopic lung lesions and significantly reduced amount of PRRSV antigen in lungs compared to the non-vaccinated VR2385-challenged positive control pigs. The nasal vaccination route appeared to be more effective in inducing protective immunity in a larger number of pigs compared to the intramuscular route. Vaccinated pigs without detectable SAVE5 viremia did not seroconvert and were fully susceptible to VR2385 challenge. Under the study conditions, the SAVE approach was successful in attenuating PRRSV strain VR2385 and protected against homologous virus challenge. Virus dosage likely needs to be adjusted to induce replication and protection in a higher percentage of vaccinated pigs.

Co-infection of porcine dendritic cells with porcine circovirus type 2a (PCV2a) and genotype II porcine reproductive and respiratory syndrome virus (PRRSV) induces CD4(+)CD25(+)FoxP3(+) T cells in vitro.

Porcine circovirus associated disease (PCVAD) is currently one of the most economically important diseases in the global swine industry. Porcine circovirus type 2 (PCV2) is the primary causative agent, however co-infection with other swine pathogens such as porcine reproductive and respiratory syndrome virus (PRRSV) is often required to induce the full spectrum of clinical PCVAD. While the specific mechanisms of viral co-infection that lead to clinical disease are not fully understood, immune modulation by the co-infecting viruses likely plays a critical role. We evaluated the ability of dendritic cells (DC) infected with PRRSV, PCV2, or both to induce regulatory T cells (T(regs)) in vitro. DCs infected with PCV2 significantly increased CD4(+)CD25(+)FoxP3(+) T(regs) (p<0.05) and DCs co-infected with PRRSV and PCV2 induced significantly higher numbers of T(regs) than with PCV2 alone (p<0.05). Cytokine analysis indicated that the induction of T(regs) by co-infected DCs may be dependent on TGF-ß and not IL-10. Our data support the immunomodulatory role of PCV2/PRRSV co-infection in the pathogenesis of PCVAD, specifically via T(reg)-mediated immunosuppression.

Multiple infection of porcine Torque teno virus in a single pig and characterization of the full-length genomic sequences of four U.S. prototype PTTV strains: implication for genotyping of PTTV.

Porcine Torque teno virus (PTTV) was recently shown to partially contribute to the experimental induction of porcine dermatitis and nephropathy syndrome and postweaning multisystemic wasting syndrome in pigs in the United States. We report here the identification of four distinct full-length genomic sequences of PTTV strains from a single pig in Virginia. Detailed analyses of the genomic organization, the degree of variability and the characteristics of conserved nucleotide and amino acid motifs of PTTV were conducted. The results showed that these four prototype U.S. strains of PTTV identified from the same pig represent distinct genotypes or subtypes and a revised classification system for PPTV is subsequently proposed. This is the first study documenting multiple PTTV infections with distinct genotypes or subtypes in a single pig. The identification of novel PTTV strains from pigs in the United States also pave the way for future disease characterization and genotyping of PTTV.