Pulmonary Specialist-Supported Health Coaching Delivered by Lay Personnel Improves Receipt of Quality Care for Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

Purpose: Half of people living with chronic obstructive pulmonary disease (COPD) do not receive high-quality, evidenced-based care as described in international guidelines. We conducted secondary data analysis of a previously published study to assess the ability of a model of lay health coaching to improve provision of guideline-based care in a primary care setting. Methods: As part of a randomized controlled trial, we recruited English- and Spanish-speaking patients with moderate to severe COPD from primary care clinics serving a low-income, predominantly African American population. Participants were randomized to receive usual care or 9 months of health coaching from primary care personnel informed by a pulmonary specialist practitioner. Outcome measures included prescription of appropriate inhaler therapy, participation in COPD-related education, engagement with specialty care, prescription of smoking cessation medications, and patient ratings of the quality of care. Results: Baseline quality measures did not differ between study arms. At 9 months, coached patients were more likely (increase of 9.3% over usual care; P=0.014) to have received guideline-based inhalers compared to those in usual care. Coached patients were more likely to engage with pulmonary specialty care (increase of 8.3% over usual care with at least 1 visit; P=0.04) and educational classes (increase of 5.3% over usual care; P=0.03). Receipt of smoking cessation medications among patients smoking at baseline in the health coaching group increased 21.1 percentage points more than in usual care, a difference near statistical significance (P=0.06). Conclusions: Health coaching may improve the provision of quality chronic illness care for conditions such as COPD.

Pilot of Brief Health Coaching Intervention to Improve Adherence to Positive Airway Pressure Therapy.

BACKGROUND: Adherence to positive airway pressure (PAP) therapies is poor, particularly among low-income populations and racial minorities. This study tested a low-resource, brief telephonic health coaching intervention to improve PAP adherence. METHODS: Post hoc analysis of a quality improvement initiative in which English- and Spanish-speaking patients from a county-based public health system were randomly assigned to receive health coaching or usual care. An unlicensed, trained health coach called patients three times to resolve barriers to adherence. A per-protocol analysis was conducted for adherence measures collected by device modem at baseline and 30 days. RESULTS: Of 131 people for whom device data were available, 56 were randomized to health coaching and 75 to usual care. At baseline, 47.3% of patients had used their device at any time in the past 30 days, with a mean of 2 hours of use per night. At 30 days, adjusting for baseline, patients in the coaching arm were more likely than usual care patients to use their device (55.4% vs. 41.3%, p = 0.03), and they increased their use for 0.4 hours over usual care (p = 0.04). CONCLUSION: This pilot study suggests that a low-cost intervention could be effective at improving PAP adherence, even in a population known to have poor adherence and among long-term PAP users with poor adherence. Future research may examine whether a higher-touch intervention or one using videoconferencing yields greater improvements. This promising intervention warrants further study.

Follow-up of incidental pulmonary nodules and association with mortality in a safety-net cohort.

Background Though incidental pulmonary nodules are common, rates of guideline-recommended surveillance and associations between surveillance and mortality are unclear. In this study, we describe adherence (categorized as complete, partial, late and none) to guideline-recommended surveillance among patients with incidental 5-8 mm pulmonary nodules and assess associations between adherence and mortality. Methods This was a retrospective cohort study of 551 patients (≥35 years) with incidental pulmonary nodules conducted from September 1, 2008 to December 31, 2016, in an integrated safety-net health network. Results Of the 551 patients, 156 (28%) had complete, 87 (16%) had partial, 93 (17%) had late and 215 (39%) had no documented surveillance. Patients were followed for a median of 5.2 years [interquartile range (IQR), 3.6-6.7 years] and 82 (15%) died during follow-up. Adjusted all-cause mortality rates ranged from 2.24 [95% confidence interval (CI), 1.24-3.25] deaths per 100 person-years for complete follow-up to 3.30 (95% CI, 2.36-4.23) for no follow-up. In multivariable models, there were no statistically significant associations between the levels of surveillance and mortality (p > 0.16 for each comparison with complete surveillance). Compared with complete surveillance, adjusted mortality rates were non-significantly increased by 0.45 deaths per 100 person-years (95% CI, -1.10 to 2.01) for partial, 0.55 (95% CI, -1.08 to 2.17) for late and 1.05 (95% CI, -0.35 to 2.45) for no surveillance. Conclusions Although guideline-recommended surveillance of small incidental pulmonary nodules was incomplete or absent in most patients, gaps in surveillance were not associated with statistically significant increases in mortality in a safety-net population.

Randomized Controlled Trial of Health Coaching for Vulnerable Patients with Chronic Obstructive Pulmonary Disease.

RATIONALE: Socioeconomically disadvantaged patients with chronic obstructive pulmonary disease (COPD) often face barriers to evidence-based care that are difficult to address in public care settings with limited resources. OBJECTIVES: To determine the benefit of health coaching for patients with moderate to severe COPD relative to usual care. METHODS: We conducted a randomized controlled trial of 9 months of health coaching versus usual care for English- or Spanish-speaking patients at least 40 years of age with moderate to severe COPD. Primary outcomes were COPD-related quality of life and the dyspnea subscale of the Chronic Respiratory Disease Questionnaire. Secondary outcomes were self-efficacy for managing COPD, exercise capacity (6-min walk test), and number of COPD exacerbations. Additional outcomes were COPD symptoms, lung function (forced expiratory volume in 1 s percent predicted), smoking status, bed days owing to COPD, quality of care (Patient Assessment of Chronic Illness Care), COPD knowledge, and symptoms of depression (Patient Health Questionnaire). Outpatient visits, emergency department visits, and hospitalizations were assessed by review of medical records. Generalized linear modeling was used to adjust for baseline values and account for clustering by clinic. RESULTS: Of 192 patients enrolled, 158 (82%) completed 9 months of follow-up. There were no significant differences between study arms for the primary or secondary outcomes. At 9 months, patients in the coached group reported better quality of care (mean Patient Assessment of Chronic Illness Care score, 3.30 vs. 3.18; adjusted P = 0.02) and were less likely to report symptoms of moderate to severe depression (Patient Health Questionnaire score, ≥15) than those in the usual care arm (6% vs. 20%; adjusted P = 0.01). During the study, patients in the coaching arm had 48% fewer hospitalizations related to COPD (0.27/patient/yr vs. 0.52/patient/yr), but this difference was not significant in the adjusted analysis. CONCLUSIONS: These results help inform expectations regarding the limitations and benefits of health coaching for patients with COPD. They may be useful to health policy experts in assessing the potential value of reimbursement and incentives for health coaching-type activities for patients with chronic disease. Clinical trial registered with www.clinicaltrials.gov (NCT02234284).

Health coaching to improve self-management and quality of life for low income patients with chronic obstructive pulmonary disease (COPD): protocol for a randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) severely hinders quality of life for those affected and is costly to the health care system. Care gaps in areas such as pharmacotherapy, inhaler technique, and knowledge of disease are prevalent, particularly for vulnerable populations served by community clinics. Non-professionally licensed health coaches have been shown to be an effective and cost-efficient solution in bridging care gaps and facilitating self-management for patients with other chronic diseases, but no research to date has explored their efficacy in improving care for people living with COPD. METHOD: This is multi-site, single blinded, randomized controlled trial evaluates the efficacy of health coaches to facilitate patient self-management of disease and improve quality of life for patients with moderate to severe COPD. Spirometry, survey, and an exercise capacity test are conducted at baseline and at 9 months. A short survey is administered by phone at 3 and 6 months post-enrollment. The nine month health coaching intervention focuses on enhancing disease understanding and symptom awareness, improving use of inhalers; making personalized plans to increase physical activity, smoking cessation, or otherwise improve disease management; and facilitating care coordination. DISCUSSION: The results of this study will provide evidence regarding the efficacy and feasibility of health coaching to improve self-management and quality of life for urban underserved patients with moderate to severe COPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02234284 . Registered 12 August 2014.

Implementation science for ambulatory care safety: a novel method to develop context-sensitive interventions to reduce quality gaps in monitoring high-risk patients.

BACKGROUND: Missed evidence-based monitoring in high-risk conditions (e.g., cancer) leads to delayed diagnosis. Current technological solutions fail to close this safety gap. In response, we aim to demonstrate a novel method to identify common vulnerabilities across clinics and generate attributes for context-flexible population-level monitoring solutions for widespread implementation to improve quality. METHODS: Based on interviews with staff in otolaryngology, pulmonary, urology, breast, and gastroenterology clinics at a large urban publicly funded health system, we applied journey mapping to co-develop a visual representation of how patients are monitored for high-risk conditions. Using a National Academies framework and context-sensitivity theory, we identified common systems vulnerabilities and developed preliminary concepts for improving the robustness for monitoring patients with high-risk conditions ("design seeds" for potential solutions). Finally, we conducted a face validity and prioritization assessment of the design seeds with the original interviewees. RESULTS: We identified five high-risk situations for potentially consequential diagnostic delays arising from suboptimal patient monitoring. All situations related to detection of cancer (head and neck, lung, prostate, breast, and colorectal). With clinic participants we created 5 journey maps, each representing specialty clinic workflow directed at evidence-based monitoring. System vulnerabilities common to the different clinics included challenges with: data systems, communications handoffs, population-level tracking, and patient activities. Clinic staff ranked 13 design seeds (e.g., keep patient list up to date, use triggered notifications) addressing these vulnerabilities. Each design seed has unique evaluation criteria for the usefulness of potential solutions developed from the seed. CONCLUSIONS: We identified and ranked 13 design seeds that characterize situations that clinicians described 'wake them up at night', and thus could reduce their anxiety, save time, and improve monitoring of high-risk patients. We anticipate that the design seed approach promotes robust and context-sensitive solutions to safety and quality problems because it provides a human-centered link between the experienced problem and various solutions that can be tested for viability. The study also demonstrates a novel integration of industrial and human factors methods (journey mapping, process tracing and design seeds) linked to implementation theory for use in designing interventions that anticipate and reduce implementation challenges.

Unexpected Role for Adaptive αßTh17 Cells in Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a devastating disorder characterized by increased alveolar permeability with no effective treatment beyond supportive care. Current mechanisms underlying ARDS focus on alveolar endothelial and epithelial injury caused by products of innate immune cells and platelets. However, the role of adaptive immune cells in ARDS remains largely unknown. In this study, we report that expansion of Ag-specific αßTh17 cells contributes to ARDS by local secretion of IL-17A, which in turn directly increases alveolar epithelial permeability. Mice with a highly restrictive defect in Ag-specific αßTh17 cells were protected from experimental ARDS induced by a single dose of endotracheal LPS. Loss of IL-17 receptor C or Ab blockade of IL-17A was similarly protective, further suggesting that IL-17A released by these cells was responsible for this effect. LPS induced a rapid and specific clonal expansion of αßTh17 cells in the lung, as determined by deep sequencing of the hypervariable CD3RßVJ region of the TCR. Our findings could be relevant to ARDS in humans, because we found significant elevation of IL-17A in bronchoalveolar lavage fluid from patients with ARDS, and rIL-17A directly increased permeability across cultured human alveolar epithelial monolayers. These results reveal a previously unexpected role for adaptive immune responses that increase alveolar permeability in ARDS and suggest that αßTh17 cells and IL-17A could be novel therapeutic targets for this currently untreatable disease.

Absence of integrin αvß3 enhances vascular leak in mice by inhibiting endothelial cortical actin formation.

RATIONALE: Sepsis and acute lung injury (ALI) have devastatingly high mortality rates. Both are associated with increased vascular leak, a process regulated by complex molecular mechanisms. OBJECTIVES: We hypothesized that integrin αvß3 could be an important determinant of vascular leak and endothelial permeability in sepsis and ALI. METHODS: ß3 subunit knockout mice were tested for lung vascular leak after endotracheal LPS, and systemic vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. Possible contributory effects of ß3 deficiency in platelets and other hematopoietic cells were excluded by bone marrow reconstitution experiments. Endothelial cells treated with αvß3 antibodies were evaluated for sphingosine-1 phosphate (S1P)­mediated alterations in barrier function, cytoskeletal arrangement, and integrin localization. MEASUREMENTS AND MAIN RESULTS: ß3 knockout mice had increased vascular leak and pulmonary edema formation after endotracheal LPS, and increased vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. In endothelial cells, αvß3 antibodies inhibited barrier-enhancing and cortical actin responses to S1P. Furthermore, S1P induced translocation of αvß3 from discrete focal adhesions to cortically distributed sites through Gi- and Rac1-mediated pathways. Cortical αvß3 localization after S1P was decreased by αvß3 antibodies, suggesting that ligation of the αvß3 with its extracellular matrix ligands is required to stabilize cortical αvß3 focal adhesions. CONCLUSIONS: Our studies identify a novel mechanism by which αvß3 mitigates increased vascular leak, a pathophysiologic function central to sepsis and ALI. These studies suggest that drugs designed to block αvß3 may have the unexpected side effect of intensifying sepsis- and ALI-associated vascular endothelial leak.

Role of small GTPases and alphavbeta5 integrin in Pseudomonas aeruginosa-induced increase in lung endothelial permeability.

Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe pneumonia associated with airspace flooding with protein-rich edema in critically ill patients. The type III secretion system is a major virulence factor and contributes to dissemination of P. aeruginosa. However, it is still unknown which particular bacterial toxin and which cellular pathways are responsible for the increase in lung endothelial permeability induced by P. aeruginosa. Thus, the first objective of this study was to determine the mechanisms by which this species causes an increase in lung endothelial permeability. The results showed that ExoS and ExoT, two of the four known P. aeruginosa type III cytotoxins, were primarily responsible for bacterium-induced increases in protein permeability across the lung endothelium via an inhibition of Rac1 and an activation of the RhoA signaling pathway. In addition, inhibition of the alphavbeta5 integrin, a central regulator of lung vascular permeability, prevented these P. aeruginosa-mediated increases in albumin flux due to endothelial permeability. Finally, prior activation of the stress protein response or adenoviral gene transfer of the inducible heat shock protein Hsp72 also inhibited the damaging effects of P. aeruginosa on the barrier function of lung endothelium. Taken together, these results demonstrate the critical role of the RhoA/alphavbeta5 integrin pathway in mediating P. aeruginosa-induced lung vascular permeability. In addition, activation of the stress protein response with pharmacologic inhibitors of Hsp90 may protect lungs against P. aeruginosa-induced permeability changes.

Protracted benign paroxysmal positional vertigo following osteotome sinus floor elevation: a case report.

Benign paroxysmal positional vertigo (BPPV) is a relatively rare condition characterized by onset of rotation dizziness triggered by head movements or change in posture. BPPV etiology includes head injury, infection, vascular disorders, surgical trauma, and idiopathic events. This report presents a case of protracted BPPV following osteotome sinus floor elevation and simultaneous implant placement. A 49-year-old female suffered intense vertigo and nausea immediately after implant placement using an osteotome sinus floor elevation procedure, especially when changing head position while sitting upright. Despite antivertigo medications, the condition did not improve. Following referral to a neurotologist, BPPV contralateral to the operation site was diagnosed 14 days after the osteotome sinus floor elevation procedure. The Epley's maneuver was then applied and, gradually, symptoms of BPPV disappeared 3 months after the implant surgery. No recurrence of BPPV was observed during further 3-month follow-up. Prevention and management of osteotome sinus floor elevation-related BPPV are reviewed in this report.

Interleukin-1beta causes acute lung injury via alphavbeta5 and alphavbeta6 integrin-dependent mechanisms.

Interleukin (IL)-1beta has previously been shown to be among the most biologically active cytokines in the lungs of patients with acute lung injury (ALI). Furthermore, there is experimental evidence that lung vascular permeability increases after short-term exposure to IL-1 protein, although the exact mechanism is unknown. Therefore, the objective of this study was to determine the mechanisms of IL-1beta-mediated increase in lung vascular permeability and pulmonary edema following transient overexpression of this cytokine in the lungs by adenoviral gene transfer. Lung vascular permeability increased with intrapulmonary IL-1beta production with a maximal effect 7 days after instillation of the adenovirus. Furthermore, inhibition of the alphavbeta6 integrin and/or transforming growth factor-beta attenuated the IL-1beta-induced ALI. The results of in vitro studies indicated that IL-1beta caused the activation of transforming growth factor-beta via RhoA/alphavbeta6 integrin-dependent mechanisms and the inhibition of the alphavbeta6 integrin and/or transforming growth factor-beta signaling completely blocked the IL-1beta-mediated protein permeability across alveolar epithelial cell monolayers. In addition, IL-1beta increased protein permeability across lung endothelial cell monolayers via RhoA- and alphavbeta5 integrin-dependent mechanisms. The final series of in vivo experiments demonstrated that pretreatment with blocking antibodies to both the alphavbeta5 and alphavbeta6 integrins had an additive protective effect against IL-1beta-induced ALI. In summary, these results demonstrate a critical role for the alphavbeta5/beta6 integrins in mediating the IL-1beta-induced ALI and indicate that these integrins could be a potentially attractive therapeutic target in ALI.

Ligation of protease-activated receptor 1 enhances alpha(v)beta6 integrin-dependent TGF-beta activation and promotes acute lung injury.

Activation of latent TGF-beta by the alpha(v)beta6 integrin is a critical step in the development of acute lung injury. However, the mechanism by which alpha(v)beta6-mediated TGF-beta activation is regulated has not been identified. We show that thrombin, and other agonists of protease-activated receptor 1 (PAR1), activate TGF-beta in an alpha(v)beta6 integrin-specific manner. This effect is PAR1 specific and is mediated by RhoA and Rho kinase. Intratracheal instillation of the PAR1-specific peptide TFLLRN increases lung edema during high-tidal-volume ventilation, and this effect is completely inhibited by a blocking antibody against the alpha(v)beta6 integrin. Instillation of TFLLRN during high-tidal-volume ventilation is associated with increased pulmonary TGF-beta activation; however, this is not observed in Itgb6-/- mice. Furthermore, Itgb6-/- mice are also protected from ventilator-induced lung edema. We also demonstrate that pulmonary edema and TGF-beta activity are similarly reduced in Par1-/- mice following bleomycin-induced lung injury. These results suggest that PAR1-mediated enhancement of alpha(v)beta6-dependent TGF-beta activation could be one mechanism by which activation of the coagulation cascade contributes to the development of acute lung injury, and they identify PAR1 and the alpha(v)beta6 integrin as potential therapeutic targets in this condition.

Transforming growth factor-beta1 decreases expression of the epithelial sodium channel alphaENaC and alveolar epithelial vectorial sodium and fluid transport via an ERK1/2-dependent mechanism.

Acute lung injury (ALI) is characterized by the flooding of the alveolar airspaces with protein-rich edema fluid and diffuse alveolar damage. We have previously reported that transforming growth factor-beta1 (TGF-beta1) is a critical mediator of ALI after intratracheal administration of bleomycin or Escherichia coli endotoxin, at least in part due to effects on lung endothelial and alveolar epithelial permeability. In the present study, we hypothesized that TGF-beta1 would also decrease vectorial ion and water transport across the distal lung epithelium. Therefore, we studied the effect of active TGF-beta1 on 22Na+ uptake across monolayers of primary rat and human alveolar type II (ATII) cells. TGF-beta1 significantly reduced the amiloride-sensitive fraction of 22Na+ uptake and fluid transport across monolayers of both rat and human ATII cells. TGF-beta1 also significantly decreased alphaENaC mRNA and protein expression and inhibited expression of a luciferase reporter downstream of the alphaENaC promoter in lung epithelial cells. The inhibitory effect of TGF-beta1 on sodium uptake and alphaENaC expression in ATII cells was mediated by activation of the MAPK, ERK1/2. Consistent with the in vitro results, TGF-beta1 inhibited the amiloride-sensitive fraction of the distal airway epithelial fluid transport in an in vivo rat model at a dose that was not associated with any change in epithelial protein permeability. These data indicate that increased TGF-beta1 activity in the distal airspaces during ALI promotes alveolar edema by reducing distal airway epithelial sodium and fluid clearance. This reduction in sodium and fluid transport is attributable in large part to a reduction in apical membrane alphaENaC expression mediated through an ERK1/2-dependent inhibition of the alphaENaC promoter activity.