Sleep architecture in patients with interstitial lung disease with and without pulmonary hypertension.

PURPOSE: Sleep disturbance is common in patients with advanced interstitial lung disease (ILD) often complicated by pulmonary hypertension (PH) and may contribute to poor quality of life. The etiology of sleep disturbance and the relationship between PH and sleep architecture in patients with ILD remains unknown. METHODS: We performed a retrospective cohort study comparing sleep architecture on polysomnography in patients with ILD with and without PH, defined as mean pulmonary artery pressure on right heart catheterization ≥ 20 mmHg. We tested the hypothesis that patients with ILD and PH would have increased wake time after sleep onset (WASO) compared to patients with ILD without PH using univariate analysis and multivariable linear regression. RESULTS: In our cohort of patients with ILD who underwent polysomnography (N = 49), patients with PH had lower total diffusion capacity for carbon monoxide (DLCO) (9.28 vs. 12.87 ml/min/mmHg, P = 0.04) and percent DLCO (39% vs. 53%, P = 0.03). On polysomnography, patients with PH had increased percentage of total sleep time with saturation < 90% (T90) (17% vs. 6%, P = 0.03), decreased N2 sleep (181 vs. 233 min, P = 0.03), decreased %N2 sleep (59% vs. 66%, P = 0.04), increased %N1 sleep (22% vs. 14%, P = 0.02), decreased sleep efficiency (62% vs. 72%, P = 0.03), and increased WASO (133 vs. 84 min, P = 0.01). In multivariable analysis, PH was associated with a 43-min increase in WASO (95% CI 6.2-80.2, P = 0.02). CONCLUSION: Patients with ILD and PH have decreased total and %N2 sleep, increased %N1 sleep, decreased sleep efficiency, and increased WASO, likely indicating increased sleep fragmentation.

Acute Opiate Overdose: An Update on Management Strategies in Emergency Department and Critical Care Unit.

BACKGROUND: Opioids are natural, semisynthetic, or synthetic substances that act on opioid receptors in the central nervous system. Clinically, they are prescribed for pain management. Opioid overdose (OOD) occurs when the central nervous system and respiratory drive are suppressed because of excessive consumption of the drug. Symptoms of OOD include drowsiness, slow breathing, pinpoint pupils, cyanosis, loss of consciousness, and death. Due to their addictive potential and easy accessibility opioid addiction is a growing problem worldwide. Emergency medical services and the emergency department often perform initial management of OOD. Thereafter, some patients require intensive care management because of respiratory failure, metabolic encephalopathy, acute kidney injury, and other organ failure. AREAS OF UNCERTAINTY: We sought to review the literature and present the most up-to-date treatment strategies of patients with acute OOD requiring critical care management. DATA SOURCES: A PubMed search was conducted to review all articles between 1950 and 2017 and the relevant articles were cited. RESULTS & CONCLUSIONS: Worldwide, approximately 69,000 people die of OOD each year, and approximately 15 million people have opioid addiction. In the United States, death from OOD has increased almost 5-fold from 2001 to 2013. OOD leading to intensive care unit admission has increased by 50% from 2009 to 2015. At the same time, the mortality associated with these admissions has doubled. The management strategies include airway management, use of reversal agents, assessing and treating coingestions and associated complications, treatment of opioid withdrawal with alpha-agonists, and psychosocial support to help with opiate addiction and withdrawal. This warrants awareness among clinicians regarding the adverse effects associated with opioid use, management strategies, and calls for a multidisciplinary approach to treating these patients.

Health Disparities in Patients with Pulmonary Arterial Hypertension: A Blueprint for Action. An Official American Thoracic Society Statement.

BACKGROUND: Health disparities have a major impact in the quality of life and clinical care received by minorities in the United States. Pulmonary arterial hypertension (PAH) is a rare cardiopulmonary disorder that affects children and adults and that, if untreated, results in premature death. The impact of health disparities in the diagnosis, treatment, and clinical outcome of patients with PAH has not been systematically investigated. OBJECTIVES: The specific goals of this research statement were to conduct a critical review of the literature concerning health disparities in PAH, identify major research gaps and prioritize direction for future research. METHODS: Literature searches from multiple reference databases were performed using medical subject headings and text words for pulmonary hypertension and health disparities. Members of the committee discussed the evidence and provided recommendations for future research. RESULTS: Few studies were found discussing the impact of health disparities in PAH. Using recent research statements focused on health disparities, the group identified six major study topics that would help address the contribution of health disparities to PAH. Representative studies in each topic were discussed and specific recommendations were made by the group concerning the most urgent questions to address in future research studies. CONCLUSIONS: At present, there are few studies that address health disparities in PAH. Given the potential adverse impact of health disparities, we recommend that research efforts be undertaken to address the topics discussed in the document. Awareness of health disparities will likely improve advocacy efforts, public health policy and the quality of care of vulnerable populations with PAH.

Diagnosing and managing scleroderma-related pulmonary arterial hypertension.

Scleroderma is an uncommon autoimmune disease of unknown cause that may affect any organ system in the body. Patients with scleroderma are prone to developing pulmonary complications, including pulmonary arterial hypertension (PAH), that are the leading cause of death in this population. This article describes scleroderma-related PAH and its diagnosis and management.

Pulmonary arterial hypertension: a current review of pharmacological management.

Pulmonary hypertension (PHTN) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance, which eventually leads to right ventricular failure and death. At present there is no cure for pulmonary arterial hypertension (PAH); however over the past decade targeted pharmaceutical options have become available for the treatment of PAH. Prior to evaluation for therapeutic options a definitive diagnosis of pulmonary arterial hypertension must be made via comprehensive physical exam and definitive diagnostic testing. Screening test of choice remains echocardiography and gold standard for definitive diagnosis is right heart catheterization. Once the establishment of a diagnosis of PAH is made therapeutic options may be a possibility based on a diagnostic algorithm and disease severity of the PAH patient. There are different classes of medications available with different mechanisms of actions which net a vasodilatory effect and improve exercise tolerance, quality of life as well and survival.

Update in primary pulmonary lymphomas.

PURPOSE OF REVIEW: Despite the fact that primary pulmonary lymphoma (PPL) is a rare lung tumour, significant advances addressing clinical features, histological diagnosis, prognostic criteria and therapeutic management of this disease have been made within the past decade. RECENT FINDINGS: Monoclonality and phenotyping of alveolar lymphocytes are suggestive of mucosa-associated lymphoid tissue (MALT). Detection of MALT-1 gene rearrangements in bronchoalveolar fluid cells using fluorescence in-situ hybridization techniques helps to confirm the diagnosis of MALT PPL. Fine needle aspiration-computed tomography guided biopsies as well as transbronchial/cryobiopsies provide adequate tissue material for histological evaluation. Recent publications also provide a better appreciation of newer chemotherapeutic approaches, including fludarabine and mitoxantrone with or without ritubximab for the treatment of MALT, as well as complete surgical resection if local disease is present. Prognostic factors influencing survival and optimal therapy for MALT have not been well defined, but the use of tumour microvascular density appears promising. SUMMARY: This review outlines the implications of recent findings for clinical practice and research progress of PPL. Larger, multicentre and well designed studies are imperative to optimize the current diagnostic and therapeutic approach for this disease.

"Saw-tooth sign" in upper airway disorders­a case report.

Spirometry flow-volume loop measurement is the screening test of choice to rule out obstructive lung diseases. Flow oscillations occasionally seen on flow volume loops, referred to as a "saw-tooth" sign, are thought to be due to an upper airway obstructive processes associated with upper airway collapsibility. Widely described in obstructive sleep apnea syndrome, flow oscillations have also been linked to many other upper airway pathologies. The mechanism by which flow oscillations occur is centered on the inspiratory and expiratory flow of air. It has been theorized that the mechanism of flow oscillations result from rapid intermittent changes in driving pressure or airway resistance. Since visual inspection of the flow volume loop can reveal presence of flow oscillations clinicians should be aware of this phenomenon and the presence of flow loop oscillations should clue physicians to rule out upper airway pathology.

Effects of pulmonary rehabilitation on Fatigue Severity Scale in patients with lung disease.

INTRODUCTION: Fatigue is a known symptom of advanced lung disease and impacts quality of life and psychological health. Many of these patients undergo pulmonary rehabilitation as part of their therapy. Understanding the effect of pulmonary rehabilitation on fatigue in these patients is important, as one may be able to design more focused rehabilitation programs. The aim of this study is to evaluate the effect of pulmonary rehabilitation on fatigue as measured by the Fatigue Severity Scale (FSS) in patients with advanced lung disease. MATERIAL AND METHODS: Patients were enrolled in a standardized 6 week pulmonary rehabilitation program. They were asked to complete questionnaires to evaluate their self-reported fatigue (FSS), and depression as measured by Geriatric Depression Scale (GDS). The GDS is a self-reported assessment tool used to identify depression in patients. The FSS is a validated instrument that indicates a perception of fatigue that might require medical intervention. Participants completed questionnaires both at baseline and after completing the standardized pulmonary rehabilitation program. Data was analyzed in Statistical Analysis System (SAS). The change in FSS was evaluated using the Wilcoxon signed-rank test. P-values < 0.05 were considered statistically significant. RESULTS: 21 patients (12 females; 9 males; mean age 64.3 ± 11.2 yrs) were considered for the study. Pre-pulmonary rehabilitation FSS scores ranged from 1.6 to 6.7 (mean score of 4.6 ± 1.7). Post pulmonary rehabilitation FSS scores ranged 1.0 to 6.2 (mean score of 3.9 ± 1.6). The median pre-rehabilitation FSS was 5.3 (inter quartile range; Q1-Q3: 3.0-6.1), and median post rehabilitation FSS was 3.9 (inter quartile range; Q1-Q3: 2.6-5.1). There was a significant decrease in FSS scores after completing pulmonary rehabilitation program (p < 0.0208). There was a decrease in GDS (pre-rehabilitation, mean: 5.5 ± 3.6; post-rehabilitation, mean: 4.2 ± 2.9), but this decrease was not statistically significant. The change in GDS correlated with the change in FSS (Spearman Correlation Coefficient 0.525, p < 0.0146). CONCLUSIONS: Patients with advanced lung disease reported a measurable component of fatigue. Participating in pulmonary rehabilitation resulted in significant improvement in patient's self-reported fatigue severity. Further studies are necessary to evaluate and design interventions to improve fatigue in in the setting of advanced lung disease.

A rare case of endobronchial and lung metastasis in basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common skin cancer, but rarely metastasizes. This article describes diagnosis and treatment of an extremely rare case of BCC metastasizing to the lung and endobronchial tissue.

Abnormal Heart Rate Recovery and Chronotropic Incompetence With Exercise in Patients With Interstitial Lung Disease With and Without Pulmonary Hypertension.

Introduction Chronotropic incompetence (CI) and heart rate (HR) recovery at one minute post-exercise (HRR1) have been proposed as indicators of autonomic imbalance. We retrospectively studied the presence of CI and HRR1 attained on cardiopulmonary exercise testing (CPET) in patients with interstitial lung disease (ILD) and those with interstitial lung disease with pulmonary hypertension (ILD-PHTN). Methods A total of 32 patients (21 had ILD alone; 11 had ILD-PHTN) underwent CPET performed per American Thoracic Society protocol on a manually-braked bicycle. HRR1 was defined as the difference between peak HR and HR after one minute post-exercise. The utilization of HR reserve recovery at peak exercise was expressed as Chronotropic Response Index (CRI) and was calculated as (peak HR-resting HR)/(220-age-resting HR). CI was defined by failure to reach 85% of the age-predicted maximum heart rate (APMHR = 200-Age) and CRI<0.80 (80%). Results VO2max was lower in patients with ILD-PHTN compared to ILD alone (14.15± 5.00 vs. 18.11± 4.48, p<0.05). Mean CRI (0.468± 0.179 versus 0.691± 0.210, p<0.05) and HRR1 (10± 7 versus 18± 9, p<0.05) were lower in patients with ILD-PHTN compared to ILD alone. Twenty out of a total of 32 patients (62.5%) met the criteria for CI. In the ILD group, 10 out of 21 patients (47.62%) and in the ILD-PHTN group 10 of 11 patients (90.90%) had CI. Conclusion Chronotropic Incompetence and abnormal heart rate recovery at one minute post-exercise are notable in patients with ILD and are more severe in patients with ILD-PHTN. These findings may contribute to our understanding of dyspnea due to these conditions.

Manifestations of pulmonary disease in adults with congenital heart disease.

Children with congenital heart disease (CHD) are more frequently living into adulthood as their survival has improved due to availability of better medical and surgical management in recent times. Management of adults with CHD is emerging as new challenge in the field of medical science. Adults surviving with CHD for longer duration have been observed to develop more complications as compared to children. It is important to recognise and treat these complications early to reduce the morbidity. Pulmonary diseases are the most common systemic complications associated with adults having CHD. These individuals are presenting to clinics or emergency for pulmonary complaints, hence, pulmonologist must be aware about the pulmonary manifestations of CHD and their management.

Ortner's syndrome: A systematic review of presentation, diagnosis and management.

Ortner's syndrome (OS), also called cardiovocal syndrome, is a rare condition hallmarked by left recurrent laryngeal nerve palsy due to underlying cardiopulmonary disease. The purpose of this review is to systemically analyze the existing literature for cases of OS to outline typical presentation, methods of diagnosis, and management of these patients. Case reports, case series, and cohort studies describing OS between 1955 and 2021 were identified. Individual manuscripts were reviewed for clinical features, presentation, and management. A total of 117 patient cases were gathered from 92 published articles. Common symptoms included hoarseness, dyspnea, cough, and dysphagia. The most common associated comorbidity was aortic aneurysm (41%), followed by pulmonary hypertension (35%), mitral stenosis (17%), and hypertension (12%). Among those who were managed via surgical intervention, 85.4% reported improvement in their hoarseness. While historically OS was associated with mitral stenosis, in recent decades, aortic aneurysms and dilation of the pulmonary artery from pulmonary hypertension have emerged as primary etiologies of OS. Therefore, OS should be considered in any patient presenting with hoarseness and history of cardiopulmonary disease. Surgical intervention in appropriate candidates resolves OS in most cases.

Macrophage migration inhibitory factor mediates hypoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a devastating disease leading to progressive hypoxemia, right ventricular failure, and death. Hypoxia can play a pivotal role in PH etiology, inducing pulmonary vessel constriction and remodeling. These events lead to increased pulmonary vessel wall thickness, elevated vascular resistance and right ventricular hypertrophy. The current study examined the association of the inflammatory cytokine macrophage migration inhibitory factor (MIF) with chronic lung disease and its role in the development of hypoxia-induced PH. We found that plasma MIF in patients with primary PH or PH secondary to interstitial lung disease (ILD) was significantly higher than in the control group (P = 0.004 and 0.007, respectively). MIF involvement with hypoxia-induced fibroblast proliferation was examined in both a human cell-line and primary mouse cells from wild-type (mif⁺/⁺) and MIF-knockout (mif⁻/⁻) mice. In vitro, hypoxia-increased MIF mRNA, extracellular MIF protein accumulation and cell proliferation. Inhibition of MIF inflammatory activity reduced hypoxia-induced cell proliferation. However, hypoxia only increased proliferation of mif⁻/⁻ cells when they were supplemented with media from mif⁺/⁺ cells. This growth increase was suppressed by MIF inhibition. In vivo, chronic exposure of mice to a normobaric atmosphere of 10% oxygen increased lung tissue expression of mRNA encoding MIF and accumulation of MIF in plasma. Inhibition of the MIF inflammatory active site, during hypoxic exposure, significantly reduced pulmonary vascular remodeling, cardiac hypertrophy and right ventricular systolic pressure. The data suggest that MIF plays a critical role in hypoxia-induced PH, and its inhibition may be beneficial in preventing the development and progression of the disease.

Comparison of obstructive sleep apnoea prevalence and severity across WHO pulmonary hypertension groups.

INTRODUCTION: Pulmonary hypertension is classified into five groups in the WHO classification system. Patients with pulmonary hypertension often have comorbid obstructive sleep apnoea (OSA), yet the prevalence and severity of OSA in each of the WHO pulmonary hypertension groups have not been well established. METHODS: To compare the prevalence and severity of OSA between WHO pulmonary hypertension groups, we performed a retrospective cohort study, including patients who had polysomnography or a home sleep study and confirmed pulmonary hypertension on right heart catheterisation. The primary outcomes of OSA prevalence and severity were measured by median apnoea hypopnea index (AHI) or respiratory event index (REI) and were compared by WHO pulmonary hypertension group. Multivariable negative binomial regression was used to evaluate the association between the outcome of OSA severity by AHI or REI and WHO group. RESULTS: Among the cohort of 132 patients, OSA was common in all WHO pulmonary hypertension groups but was most common and most severe in WHO group II pulmonary hypertension. Median AHI or REI in WHO group II was 12.0 events/hour compared with 2.8 in group I, 3.7 in group III, 10.0 in group IV and 6.4 in group V. Multivariable negative binomial regression showed about a twofold increase in AHI or REI in WHO group II compared with WHO group I pulmonary hypertension. DISCUSSION: Our findings demonstrate that OSA deserves greater consideration as a treatable comorbidity that may affect pulmonary haemodynamics and quality of life in patients with pulmonary hypertension across all WHO groups.

Correlation of pulmonary hypertension severity with metrics of comorbid sleep-disordered breathing.

PURPOSE: We performed nocturnal polysomnography in patients with pulmonary hypertension (PH) of varying etiologies to determine the association of metrics describing sleep-disordered breathing (SDB) with measures of PH severity. METHODS: Consecutive patients referred for evaluation of dyspnea on exertion and elevated pulmonary arterial pressure >30 mmHg on echocardiography, who underwent right and left heart catheterization and polysomnography, were included. Patients were not pre-selected for symptoms of sleep-disordered breathing. RESULTS: Twenty-eight patients including 22 females and six males with a mean age of 55.2 ± 11.9 years were evaluated. Etiologies of PH were idiopathic (32%) and PH associated with other diseases (68%). Most were World Health Organization (WHO) Functional class II (39%) and III (39%). The group mean pulmonary arterial pressure (mPAP) was 40.9 ± 15.1 mmHg. Diurnal resting and exercise arterial oxygen saturations (SaO(2)) were 94.9 ± 3.7% and 88.3 ± 8.9%. The mean apnea-hypopnea index (AHI) was 11.4 ± 19.8/h; 50% of all patients had an AHI ≥ 5/h; 30.6 ± 36.0% of total sleep time was spent with SaO(2) < 90% (T90%); 66% of subjects with an AHI ≥ 5/h of sleep reported snoring, and 60% noted daytime somnolence; however, only 29% had an Epworth Sleepiness Scale ≥10. Right atrial pressure and mPAP were significantly correlated with AHI and T90%. The best predictive model relating PH severity to metrics of SDB was a highly significant association (p = 0.005) between mPAP and a linear combination of AHI and T90%. CONCLUSIONS: SDB comprised of obstructive apneas, hypopneas, and nocturnal hypoxemia is prevalent in PH and cannot be accurately predicted by sleep apnea signs and symptoms or diurnal rest and exercise SaO(2). The association of AHI and T90% with mPAP suggests a potential relationship between the pathophysiology of sleep-disordered breathing and PH.

Bronchoscopy and endobronchial disease in patients with human immunodeficiency virus infection.

The natural history of human immunodeficiency virus (HIV) infection has been significantly altered since the advent of antiretroviral therapy (ART). However, lung diseases are still common in these patients. This makes flexible fibreoptic bronchoscopy a valuable diagnostic tool. Knowledge of the visual appearance of various diseases would be of utmost importance to the bronchoscopist. Timely recognition of the endobronchial appearance of these diseases can narrow the differential diagnosis and potentially mitigate an avoidable delay in the diagnosis.

Enlarged pulmonary artery on computed tomography and respiratory failure in sickle cell disease acute chest syndrome.

Predicting the severity of acute chest syndrome is an important research priority in sickle cell disease. In this retrospective study of patients with acute chest syndrome, an enlarged pulmonary artery on computed tomography was associated with severe respiratory failure defined by the need for either noninvasive or mechanical ventilation.

The Usefulness of Chest CT Imaging in Patients With Suspected or Diagnosed COVID-19: A Review of Literature.

The COVID-19 pandemic has had devastating medical and economic consequences globally. The severity of COVID-19 is related, in a large measure, to the extent of pulmonary involvement. The role of chest CT imaging in the management of patients with COVID-19 has evolved since the onset of the pandemic. Specifically, the description of CT scan findings, use of chest CT imaging in various acute and subacute settings, and its usefulness in predicting chronic disease have been defined better. We performed a review of published data on CT scans in patients with COVID-19. A summary of the range of imaging findings, from typical to less common abnormalities, is provided. Familiarity with these findings may facilitate the diagnosis and management of this disease. A comparison of sensitivity and specificity of chest CT imaging with reverse-transcriptase polymerase chain reaction testing highlights the potential role of CT imaging in difficult-to-diagnose cases of COVID-19. The usefulness of CT imaging to assess prognosis, to guide management, and to identify acute pulmonary complications associated with SARS-CoV-2 infection is highlighted. Beyond the acute stage, it is important for clinicians to recognize pulmonary parenchymal abnormalities, progressive fibrotic lung disease, and vascular changes that may be responsible for persistent respiratory symptoms. A large collection of multi-institutional images were included to elucidate the CT scan findings described.