Effects of High Frequency Chest Wall Oscillation (HFCWO) on Clinical Symptoms in COPD.

Background: Mucociliary clearance plays a critical role in pulmonary host defense. Abnormal mucociliary clearance contributes to the pathogenesis of pulmonary disorders, including COPD. In bronchiectasis, treatments targeting mucus obstruction in the airways include the use of high frequency chest wall oscillation (HFCWO) therapy. This prospective outcome based study was designed to investigate the changes in symptoms and quality of life (QOL) to measure the effect of adjunctive HFCWO therapy to standard of care therapy for patients with COPD. Research Question: When HFCWO is indicated and used as intended, will the quality of life for those patients with COPD improve and sustain improvement. Study Design and Methods: We conducted a prospective, openl-label, observational study in COPD patients without concomitant bronchiectasis. Participants had assessments of QOL at baseline (day 0) and then at 30 and 90 days after initiation of HFCWO therapy. The St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) was employed and longitudinally followed at each timepoint. Paired t-tests were used to compare means between each time points adjusted for multiple comparisons. A linear mixed model for the analysis of longitudinal data was then constructed to determine the simultaneous contribution of race, gender, ethnicity, time, and selected interactions in the primary outcome of change in SGRQ-C across 0, 30, and 90 days. Results: The cohort of patients (n=102) demonstrated a significant reduction in the SGRQ-C at 30 and sustained at 90 days compared to baseline. In addition, two component scores of the SGRQ-C questionnaire ("Symptoms" and Impacts") were significantly reduced at 30 and 90 days. Interpretation: This prospective, observational study demonstrates statistically significant and clinically favorable responses to HFCWO as an adjunctive therapy for patients with a primary diagnosis of COPD without concomitant bronchiectasis. Results of this study inform the design of additional additional studies of HFCWO to prove efficacy inCOPD patients.

Reduction of Endotracheal Tube Biofilms Using Antimicrobial Photodynamic Therapy.

BACKGROUND: Ventilator-associated pneumonia (VAP) is reported to occur in 12 to 25% of patients who require mechanical ventilation with a mortality rate of 24 to 71%. The endotracheal (ET) tube has long been recognized as a major factor in the development of VAP since biofilm harbored within the ET tube become dislodged during mechanical ventilation and have direct access to the lungs. The objective of this study was to demonstrate the safety and effectiveness of a non-invasive antimicrobial photodynamic therapy (aPDT) treatment method of eradicating antibiotic resistant biofilms from ET tubes in an in vitro model. METHODS: Antibiotic resistant polymicrobial biofilms of Pseudomonas aerugenosa and MRSA were grown in ET tubes and treated, under standard ventilator conditions, with a methylene blue (MB) photosensitizer and 664nm non-thermal activating light. Cultures of the lumen of the ET tube were obtained before and after light treatment to determine efficacy of biofilm reduction. RESULTS: The in vitro ET tube biofilm study demonstrated that aPDT reduced the ET tube polymicrobial biofilm by >99.9% (p<0.05%) after a single treatment. CONCLUSIONS: MB aPDT can effectively treat polymicrobial antibiotic resistant biofilms in an ET tube.

Antimicrobial photodynamic therapy treatment of chronic recurrent sinusitis biofilms.

BACKGROUND: Chronic recurrent sinusitis (CRS) is an inflammatory disease of the facial sinuses and nasal passages that is defined as lasting longer than 12 weeks or occurring more than 4 times per year with symptoms usually lasting more than 20 days. The National Institute for Health Statistics estimates that CRS is one of the most common chronic conditions in the United States, affecting an estimated 37 million Americans. The potential etiologies of CRS include bacteria, viruses, allergies, fungi, superantigens, and microbial biofilms. In clinical practice there is a significant subpopulation of patients with CRS who remain resistant to cure despite rigorous treatment regimens including surgery, allergy therapy, and prolonged antibiotic therapy. The reason for treatment failure is thought to be related to the destruction of the sinus mucociliary defense by the chronic sinus infection resulting in the development of secondary antibiotic-resistant microbial colonization of the sinuses and biofilm formation. Antimicrobial photodynamic therapy (aPDT) is a nonantibiotic broad-spectrum antimicrobial treatment that has been demonstrated to eradicate antibiotic-resistant bacteria and biofilms. The objective of this study was to demonstrate the effectiveness of a noninvasive aPDT treatment method of eradicating antibiotic resistant biofilms/microorganisms known to cause CRS in an in vitro model. METHODS: Antibiotic-resistant planktonic bacteria and fungi and polymicrobial biofilms of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) were grown on silastic sheets and treated with a methylene blue photosensitizer and 670 nm non-thermal-activating light. Cultures of the planktonic microorganisms and biofilms were obtained before and after light treatment to determine efficacy of planktonic bacteria and biofilm reduction. RESULTS: The in vitro CRS planktonic microorganism and biofilm study demonstrated that aPDT reduced the CRS polymicrobial biofilm by >99.9% after a single treatment. CONCLUSION: aPDT can effectively treat CRS polymicrobial antibiotic-resistant bacteria, fungi, and biofilms in vivo. Human clinical studies are currently planned to assess the safety and efficacy of this treatment for CRS.

Effect of Ca+ on the photobactericidal efficacy of methylene blue and toluidine blue against gram-negative bacteria and the dye affinity for lipopolysaccharides.

BACKGROUND AND OBJECTIVES: Methylene blue (MB) and toluidine blue (TB) form metachromatic complexes with lipopolysaccharides (LPS). The greater photobactericidal efficacy of TB may be explained by its affinity for LPS. This study aims to elucidate the difference in photobactericidal efficacies between the dyes using Ca(2+) as a competitor for dye-binding sites on the bacterial outer membrane. STUDY DESIGN/MATERIALS AND METHODS: Fixed dye concentration solutions with gram-negative bacteria and increasing concentrations of CaCl(2) were exposed to red laser light. Bacterial survival and spectrophotometry were used to describe the effect of Ca(2+) on dye interaction with bacteria and LPS. RESULTS: MB-mediated photokilling was inhibited more significantly than that of TB. CaCl(2) inhibited dye photobleaching and suppressed the metachromatic reaction between the dyes and LPS, in particular TB. CONCLUSIONS: CaCl(2) inhibits bacterial photokilling by binding with LPS, as well as other anionic polymers including outer membrane proteins. LPS is chiefly involved in TB-mediated photokilling, whereas outer membrane proteins probably are more involved in MB-mediated photokilling.