Patients\u27 Perceptions and Patient-Reported Outcomes in Progressive-Fibrosing Interstitial Lung Diseases

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be used to assess an array of constructs affected by a disease or the interventions implemented to treat it. Here, we review the impact of ILD that may present with a progressive-fibrosing phenotype on patients\u27 lives and examine how PROs have been used to measure that impact and the effectiveness of therapeutic interventions

Patients\u27 perceptions and patient-reported outcomes in progressive-fibrosing interstitial lung diseases

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be used to assess an array of constructs affected by a disease or the interventions implemented to treat it. Here, we review the impact of ILD that may present with a progressive-fibrosing phenotype on patients\u27 lives and examine how PROs have been used to measure that impact and the effectiveness of therapeutic interventions

Patients\u27 Perceptions and Patient-Reported Outcomes in Progressive-Fibrosing Interstitial Lung Diseases

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be used to assess an array of constructs affected by a disease or the interventions implemented to treat it. Here, we review the impact of ILD that may present with a progressive-fibrosing phenotype on patients\u27 lives and examine how PROs have been used to measure that impact and the effectiveness of therapeutic interventions

Penicillum marneffei presenting as a pneumonia and obstructive airway disease exacerbation.

Penicillum marneffei, a pathogenic thermally dimorphic fungi causing pulmonary infection, was initially described in HIV-infected patients. The incidence rate has decreased with improved diagnostic testing for HIV and availability of highly active anti-retroviral therapy. Recently, the emergence of this pathogen in patients with underlying primary or secondary immunosuppression has been described. We share a case of Penicillum species causing infection in a patient with previously controlled IgG deficiency. Case presentation: A 52 year old female patient with history of prior tobacco use, chronic obstructive pulmonary disease, asthma, allergic rhinitis, prior eosinophilic pneumonia, and IgG deficiency on subcutaneous IgG replacement presented to the emergency department with worsening shortness of breath, cough, subjective fevers and night sweats. Of note, the patient had suffered recurrent obstructive airways disease exacerbations over the preceding three months and was treated with chronic intermittent steroids and antibiotics with partial improvement. Her physical examination revealed new hypoxia and wheezing. Her workup was notable for a normal white count, an absolute eosinophil count of 300 cells/microL, no lymphopenia, normal IgG levels, a CD4 count of 700 cell/ul, and a negative HIV ELISA. Computed Tomography (CT) of the chest showed bilateral bronchial wall thickening, tree-in-bud opacities, and ground glass opacities. Bronchoscopy revealed purulent secretions emerging from the right upper lobe. Her bronchoalveolar lavage cultures initially grew 100,000 Streptococcus colonies for which the patient was treated with levofloxacin for 14 days with mild improvement in symptoms. Fungal cultures subsequently grew Penicillum species. She was prescribed itraconazole with improvement in dyspnea, cough and low grade fevers over the following week. Chest CT four weeks later showed resolution of the radiographic abnormalities. Discussion: Penicillium marneffei infection has been reported in 15 cases of non-HIV-infected patients with autoimmune disease. The predisposing factor may be either the underlying autoimmune disease or its treatment. Infection occurs when patients receive treatment with T lymphocyte depleting drugs such as steroids, cyclosporine, azathioprine, tacrolimus and mycophenolate mofetil. Our patient received intermittent courses of steroids for management of obstructive airways disease exacerbations, which likely increased her susceptibility to infection with Penicillium species. We present this case to draw heightened awareness of this serious infection in iatrogenically immunosuppressed patients

Rothia mucilaginosa pneumonia complicating interstitial lung disease.

Rothia mucilaginosa is a gram-positive coccus found in the human oropharynx and upper respiratory tract which can cause opportunistic infections in hosts who are immunocompromised or have impaired pulmonary defense. We share a rare case of Rothia mucilaginosa pneumonia identified during workup of suspected Hypersensitivity Pneumonitis. Case Report A 63 year-old male with a remote history of tobacco use, nonalcoholic steatohepatitis-related cirrhosis, post liver transplant 1 year prior complicated by dermatologic and gastrointestinal graft-vs-host disease (GVHD) presented to the Interstitial Lung Disease (ILD) clinic with progressive dyspnea with exercise, nonproductive cough, and fatigue. He denied fevers, chills or night sweats. His anti-rejection regimen consisted of tacrolimus. Prednisone had been tapered off 2 months prior to presentation. His exposures included frequent hot tub use. Cardiopulmonary physical exam was only remarkable for chronic lower extremity edema. Pulmonary function tests (PFTs) revealed a forced vital capacity (FVC) of 4.12 L (77% predicted) and diffusion capacity (DLCO) 16.4 mL/mmHg/min (56% predicted), both significantly lower from 1 year prior. Echocardiogram did not show evidence of pulmonary hypertension. There was no neutropenia or lymphopenia. A mildly elevated ANA and low titer myeloperoxidase antibody were suspected to be GVDH related per Rheumatology. High resolution chest computed tomography (HRCT) showed progression of peripheral reticulation, scattered septal thickening, ground glass opacities, and lower lobe air-trapping compared to CT prior to liver transplant, lowering suspicion of tacrolimus-induced toxicity or GVHD. The patient was instructed to avoid hot tub use for suspected Hypersensitivity Pneumonitis. Bronchoscopy revealed Rothia mucilaginosa on bronchoalveolar lavage and evidence of acute and chronic interstitial inflammation on transbronchial biopsies. On reevaluation, he recalled dental work in the months prior to presentation. He was prescribed a 12-week course of Penicillin 500 mg every 6 hours. He reported improvement in dyspnea and cough within 1 week of starting antibiotics. He abstained from further hot tub use. Eight weeks later, the FVC and DLCO significantly improved, and HRCT showed improvement in ground glass opacities. Discussion Rothia mucilaginosa pneumonia has been reported in patients with hematologic malignancies, neutropenia with central venous catheters, and impaired pulmonary clearance. Third generation cephalosporins, high dose Ampicillin, Vancomycin, Rifampicin, Chloramphenicol, and Penicillin are reported to have activity against Rothia. The improvement in pulmonary infiltrates could be attributed to removal of hot tub exposure alone. However, the symptomatic improvement shortly after initiation of antibiotics points to the contribution of Rothia pneumonia to this presentation of ILD

A rare case of antisynthetase syndrome presented with cardiogenic shock as an initial presentation.

Antisynthetase syndrome is a rare autoimmune disease associated with interstitial lung disease (ILD), inflammatory myopathy, and inflammatory polyarthritis. A 62-year-old female who presented to the hospital with 4 months\u27 history of progressive dyspnea, orthopnea, lower extremity edema, generalized muscle pains and weakness, and bilateral joint pains involving her hands, shoulders and knees. On presentation, her clinical picture was consistent with cardiogenic shock and right ventricular (RV) failure. The patient was afebrile but hypotensive and hypoxemic. Physical exam was significant for cold extremities, bilateral lower extremity edema, bilateral diffuse inspiratory crackles on chest auscultation and jugular venous pulsations. Her chest X-ray showed cardiomegaly with bilateral diffuse interstitial infiltrates and bilateral small pleural effusion. Her laboratory investigations demonstrated an elevated BNP 1241 pg/ml, troponin 0.13 ng/ml, elevated liver enzymes, elevated creatinine 1.5 mg/dl, and mixed venous saturation 53%. Echocardiography showed severe RV enlargement with RV systolic dysfunction, flattening of the interventricular septum and estimated pulmonary arterial systolic pressure 60 mmHg. Intravenous Milrinone infusion was initiated for the suspected cardiogenic shock. The patient had adequate diuresis then right heart catheterization demonstrating mean pulmonary artery pressure 36 mmHg, pulmonary capillary wedge pressure (PCWP)14 mmHg with normal cardiac index while on Milrinone infusion. After achieving euvolemic status confirmed by the PCWP tracing and weaning off Milrinone, Chest CT scan showed persistent bilateral ground glass opacities and interlobular septal thickening, as well as bronchiectatic changes suspecting an underlying ILD. Further workup was consistent with the diagnosis of Antisynthetase syndrome (elevated ANA titers 1:640 {speckled pattern}, elevated CPK and Aldolase levels, Positive Mi-2 antibodies, inflammatory myositis confirmed by muscle biopsy) and she could not tolerate lung biopsy. It was suspected that her RV failure and cardiogenic shock are due to severe pulmonary hypertension (World Health Organization groups I, III) secondary to pulmonary arterial vasculopathy from her autoimmune disease and underlying ILD. Her dyspnea, fatigue, severity of hypoxia, severity of restrictive defect and CPK all improved with systemic steroids and continued diuresis. We share this rare presentation of antisynthetase syndrome with cardiogenic shock to highlight the need for appropriate diagnosis of an underlying systemic disease in management of such critical conditions when presented to the ICU

Shrinking lung syndrome with hypercapneic respiratory failure responsive to mycophenolate mofetil and systemic steroids.

Shrinking Lung Syndrome (SLS) is a rare complication of Systemic Lupus Erythematosus (SLE) characterized by progressive dyspnea, pleuritic chest pain, diaphragmatic elevation, and a restrictive defect without parenchymal abnormalities. We present a case of SLS to highlight this rare manifestation of SLE and potential modes of therapy. Case Report A 35 year old woman with SLE with manifestations of Raynaud\u27s syndrome, serositis with prior pericardiocentesis, oral ulcers, lower extremity ulcers, and antiphospholipid antibody syndrome presented to the hospital with severe progressive dyspnea, pleuritic left chest pain, and 1 year of nonproductive cough. Her immunosuppression consisted of Mycophenolate Mofetil (MMF) 1000 mg twice daily and prednisone 20 mg daily for three months. Physical exam was remarkable for tachypnea, tachycardia, exertional hypoxia, bibasilar diminished breath sounds without wheeze or crackles, holosystolic murmur with regular rate and rhythm, and healing lower extremity ulcers. ABG showed CO2 56 and pH 7.34. Laboratory values were notable for C3 84(L), C4 29, Anti-dsDNA negative, sedimentation rate 45 (H), C-reactive protein 6.7(H), and room air arterial blood gas pH 7.34, pCO2 56, pO2 99.1. Chest CT revealed bibasilar atelectasis with pleural thickening without pulmonary artery filling defects. Echocardiogram showed a normal ejection fraction and pulmonary artery pressure. Pulmonary function tests (PFTs) showed severe restriction with impaired gas transfer. She was diagnosed with SLS on the basis of severe restriction without parenchymal abnormalities. Bi-level positive airway pressure (BIPAP) was prescribed for chronic hypercapneic respiratory failure and obstructive sleep apnea (apnea hypopnea index of 10). The MMF dose was increased to 1500 mg BID, and prednisone was later slowly weaned. Her dyspnea, left-sided chest pain, and severity of restriction significantly improved. Her exertional hypoxia and chronic hypercapneic respiratory failure resolved and have not recurred during 3 months off BIPAP. Discussion The proposed mechanism of SLS is diaphragmatic myositis or myopathy causing elevation of the diaphragms and decreasing lung volumes. Chronic pleural inflammation may also impair deep inspiration leading to parenchymal reorganization and decline in lung compliance. While data are limited, immunosuppressive therapy may improve both symptoms and pulmonary function. Noninvasive ventilation (NIV) provides ventilatory support in patients with chronic hypercapneic respiratory failure. In conclusion, we share a presentation of SLS with chronic hypercapneic respiratory failure to raise awareness of potential treatment with MMF and systemic steroids. (Table Presented)

Optimization of patient-specific inhaler regimens: A pharmacy-pulmonology collaborative pilot program in the ambulatory care setting

Inhaler technique is an important component of optimal control of asthma and COPD. Evidence suggests that 50- 90% of patients use their inhalers improperly and that detailed training alone is insufficient for maintaining correct inhaler technique with each device. Currently, there are no objective assessments or treatment guidelines to direct clinicians in selecting the optimal inhaler delivery device. The purpose of this pilot study is to evaluate the effects of the addition of a pulmonary clinic pharmacist to assess inhaler technique and to optimize inhaler regimens using a Vitalograph Aerosol Inhalation Monitor™ (VAIM). METHODS: This prospective, observational cohort study enrolled patients seen in the outpatient pulmonary clinic at Henry Ford Hospital (HFH) from October 2015 to March 2016. Patients were included if they had a diagnosis of COPD or asthma, spoke English, and were 18 years of age or older. Patients were excluded if they presented for imaging results review, had a tracheostomy, or had a diagnosis of interstitial lung disease, sarcoidosis, or lung cancer. A pharmacist provided inhaler regimen recommendations to physicians based on objective VAIM assessments to help develop an individualized therapy plan. If the recommendations were accepted, the pharmacist then reviewed any inhaler changes with the patient. Follow-up phone calls were made at one and four weeks after the initial visit. The primary endpoint was asthma or COPD control as defined by changes in asthma control test (ACT) or COPD assessment test (CAT) scores, patient-reported symptoms, and weekly rescue inhaler use. Secondary endpoints included changes in patient adherence as measured by the Morisky Medication Adherence Scale (MMAS4) and to describe the utility of the VAIM in objectively assessing inhaler technique. RESULTS: A total of 53 patients with COPD and/or asthma were screened; 44 patients met inclusion criteria. The majority of patients were female (59%) with a diagnosis of COPD and a median age of 60 years. Eighty-one percent of patients were interacting with a clinical pharmacist in the pulmonary clinic for the first time. While 72% of patients were on appropriate therapy per GINA and GOLD clinical guidelines, 27 (61%) patients received a recommendation to change inhaler devices based on VAIM assessments. Following pharmacist intervention and change in inhaler devices, rescue inhaler use decreased from 24.4 times per week at baseline to 10.6 times per week at week 4 (p=0.0019); CAT scores (n=19) improved from 24.4 at baseline to 20.2 at week 4 (p=0.0079); and ACT scores (n=12) improved from 12.3 at baseline to 16.6 at week 4 (p=0.04). The MMAS4 score improved from 0.8 to 0.4 at week 4 (p = 0.0217). CONCLUSIONS: A pharmacist-performed objective assessment of inhaler technique and subsequent pharmacologic recommendations added to a routine pulmonary clinic visit are not only feasible, but also may improve patient outcomes

A longitudinal analysis of pharmacist-driven inhaler optimization in the ambulatory care setting.

The overall prevalence of correct inhaler technique remains poor, and education alone does not correct poor technique. An important component that is often missing from selection of a pulmonary regimen is an objective assessment of patients\u27 inhaler technique. Pharmacists can play a role in the selection of appropriate pulmonary regimen that matches patients\u27 respiratory abilities using the Vitalograph Aerosol Inhalation Monitor™ (AIM). Methods: This one-group, pretest-posttest quasi-experimental study enrolled patients with asthma and COPD who presented to Henry Ford Hospital Pulmonary Clinic from June 2016 to March 2017. Patients met with a pharmacist who provided a bundle of services including an inhaler technique assessment with the AIM. Based on the patient\u27s performance, the pharmacist developed patientspecific plans. Follow up phone calls were made one, four, and twelve weeks after the initial visit. The primary outcome was change in ACT or CAT at four and twelve weeks compared to baseline. Secondary outcomes included change in patient reported weekly rescue medication use and change in adherence using MMAS-4 scores. An analysis of patients seen by a pulmonologist during the same period, who had at least two documented ACT or CAT scores were randomly selected for comparison. Results: A total 75 patients met inclusion criteria. Based on the AIM assessment, 89% of patients were not on an appropriate device. The most common recommendation made by the pharmacist was to change to a fully nebulized regimen. Patients with asthma had a significant improvement in their ACT scores from baseline to four weeks (12.1 vs 16.3, p\u3c0.01) and baseline to twelve weeks (12.5 vs 17.1, p\u3c0.01). Patients with COPD had a non-significant improvement in their CAT scores from baseline to week four (22.7 vs 20.7, p=0.19), but a significant improvement from baseline to week twelve (22.7 vs 20.1, p=0.02). The historical control group did not have a significant improvements in their ACT and CAT scores. Patient-reported rescue inhaler use improved at week one (20.6 vs 13.3, p\u3c0.01), four (22.1 vs 15.5, p=0.06), and twelve (21.6 vs 12.5, p\u3c0.01). The MMAS-4 scores did not significantly improve at week four or twelve. Conclusion: Incorporating an objective assessment of inhaler technique into a pulmonary clinic visit by a pharmacist may help improve asthma and COPD control though twelve weeks. Future research into objectively assessing inhaler technique in order to optimize patient\u27s pulmonary regimens is warranted

A longitudinal analysis of pharmacist-driven inhaler optimization in the ambulatory care setting.

Rationale: The overall prevalence of correct inhaler technique remains poor, and education alone does not correct poor technique. An important component that is often missing from selection of a pulmonary regimen is an objective assessment of patients\u27 inhaler technique. Pharmacists can play a role in the selection of appropriate pulmonary regimen that matches patients\u27 respiratory abilities using the Vitalograph Aerosol Inhalation Monitor™ (AIM). Methods: This one-group, pretest-posttest quasi-experimental study enrolled patients with asthma and COPD who presented to Henry Ford Hospital Pulmonary Clinic from June 2016 to March 2017. Patients met with a pharmacist who provided a bundle of services including an inhaler technique assessment with the AIM. Based on the patient\u27s performance, the pharmacist developed patientspecific plans. Follow up phone calls were made one, four, and twelve weeks after the initial visit. The primary outcome was change in ACT or CAT at four and twelve weeks compared to baseline. Secondary outcomes included change in patient reported weekly rescue medication use and change in adherence using MMAS-4 scores. An analysis of patients seen by a pulmonologist during the same period, who had at least two documented ACT or CAT scores were randomly selected for comparison. Results: A total 75 patients met inclusion criteria. Based on the AIM assessment, 89% of patients were not on an appropriate device. The most common recommendation made by the pharmacist was to change to a fully nebulized regimen. Patients with asthma had a significant improvement in their ACT scores from baseline to four weeks (12.1 vs 16.3, p\u3c0.01) and baseline to twelve weeks (12.5 vs 17.1, p\u3c0.01). Patients with COPD had a non-significant improvement in their CAT scores from baseline to week four (22.7 vs 20.7, p=0.19), but a significant improvement from baseline to week twelve (22.7 vs 20.1, p=0.02). The historical control group did not have a significant improvements in their ACT and CAT scores. Patient-reported rescue inhaler use improved at week one (20.6 vs 13.3, p\u3c0.01), four (22.1 vs 15.5, p=0.06), and twelve (21.6 vs 12.5, p\u3c0.01). The MMAS-4 scores did not significantly improve at week four or twelve. Conclusion: Incorporating an objective assessment of inhaler technique into a pulmonary clinic visit by a pharmacist may help improve asthma and COPD control though twelve weeks. Future research into objectively assessing inhaler technique in order to optimize patient\u27s pulmonary regimens is warranted