Rapidly progressive fatal hypoxia in a young woman.

We present a rare cause of pulmonary arterial hypertension in a 29-year-old woman with rapidly progressive and fatal hypoxia. Subsequent workup revealed classic radiological findings and pathologic confirmation of pulmonary veno-occlusive disease.

A 55-Year-Old Woman With Frequent Pulmonary Exacerbations and Endobronchial Lesions.

CASE PRESENTATION: A 55-year-old woman with COPD, heart failure with preserved ejection fraction (congestive heart failure), diabetes mellitus, and hypertension presented with baseline dyspnea at rest that had worsened over the last week. She reported associated runny nose, congestion, and cough productive of green sputum. She smoked six cigarettes per day and denied alcohol, drugs, or occupational exposure. She was admitted and initiated on treatment for acute exacerbation of COPD; however, her condition did not improve with steroid, ceftriaxone, and nebulized albuterol and budesonide treatments. She had been diagnosed with asthma and COPD without ever undergoing pulmonary function testing. She presented 11 times to the ED with six hospital admissions in the last 1.5 years for worsening dyspnea at rest, wheezing, and lower extremity edema deemed secondary to exacerbation of her COPD or congestive heart failure. She reported medication compliance, which included fluticasone-vilanterol, tiotropium bromide, and furosemide. She repeatedly demonstrated mild vascular congestion on imaging without hyperinflation, a normal to mildly elevated brain natriuretic peptide (<10 to 200 pg/mL), and dyspnea without hypoxia. She was treated normally for both COPD and congestive heart failure exacerbations simultaneously with methylprednisolone, albuterol, and furosemide with rapid improvement over the course of 1 to 2 days. No significant improvement was noted with steroid therapy, despite receiving them as an inpatient and outpatient. At the time of discharge, her symptoms would be at her baseline.

Pulmonary hyalinising granuloma: a rare and elusive cause of multiple lung nodules.

A 72-year-old woman was referred with incidentally detected multiple lung nodules, one of which was identified as 18F-fluorodeoxyglucose (FDG)-avid on positron emission tomography. Extensive workup followed, including numerous radiographs, surveillance scans and a CT-guided biopsy which demonstrated chronic inflammation only. Following a wedge-resection, a diagnosis of pulmonary hyalinising granuloma (PHG) was made. PHG is a cause of FDG-avid single or multiple pulmonary nodules and can mimic lung cancer or metastatic disease radiologically. The diagnosis is often difficult to make with minimally invasive techniques such as needle-guided biopsies which do not tend to yield the diagnosis and requires surgical resection for definitive diagnosis and exclusion of malignancy.

Syphilitic aortitis: still a current common cause of aneurysm of the tubular portion of ascending aorta.

Aortic syphilis today is infrequently diagnosed clinically. Described herein are findings in 5 women who had resection of a fusiform aneurysm of the tubular portion of ascending aorta, and examination of the wall of the aneurysm disclosed classic features of aortic syphilis. The 5 patients were among 36 who had ascending aortic operations at Baylor University Medical Center in Dallas in 2018 and early 2019. Syphilitic aneurysm in each spared the sinus portion and involved diffusely the tubular portion of ascending aorta, beginning at the sinotubular junction. The aneurysmal wall was thicker than normal because of thickening of both intima and adventitia. The latter contained foci of lymphocytes and plasmacytes and thickened and narrowed vasa vasora. The media was disrupted by fibrous scars, which weakened the integrity of the aorta. Aortitis of the tubular portion of ascending aorta in syphilis is a diffuse process, but often is mistakenly called "atherosclerosis" which, when present in this portion of aorta, can be extensive but is focal. Aortic syphilis is important to diagnose so that patients can receive antibiotic therapy to delay, prevent, or treat neurosyphilis, a common accompaniment of aortic syphilis.

Ascending aortic thrombus with multiple emboli associated with COVID-19.

Coronavirus disease 2019 (COVID-19) initiates a hypercoagulable state and causes thrombotic complications. A presentation of multiple thromboembolic events without an underlying source should raise suspicion for COVID-19 hypercoagulability. We describe a patient with an ascending aortic thrombus resulting in multiple emboli treated by multiple modalities.

Pseudoaneurysm of the Ascending Aorta at the Cannulation Site Diagnosed More Than Four Decades After Repair of Ventricular Septal Defect.

Described herein is a 69-year-old woman who developed a large saccular aortic aneurysm at a previous cannulation site for repair of a ventricular septal defect at age 25 years. The aneurysm was resected and proved histologically to be a false one. The long interval between operations (44 years) exceeds those reported previously.

Imaging of acute pulmonary embolism: an update.

Imaging plays an important role in the evaluation and management of acute pulmonary embolism (PE). Computed tomography (CT) pulmonary angiography (CTPA) is the current standard of care and provides accurate diagnosis with rapid turnaround time. CT also provides information on other potential causes of acute chest pain. With dual-energy CT, lung perfusion abnormalities can also be detected and quantified. Chest radiograph has limited utility, occasionally showing findings of PE or infarction, but is useful in evaluating other potential causes of chest pain. Ventilation-perfusion (VQ) scan demonstrates ventilation-perfusion mismatches in these patients, with several classification schemes, typically ranging from normal to high. Magnetic resonance imaging (MRI) also provides accurate diagnosis, but is available in only specialized centers and requires higher levels of expertise. Catheter pulmonary angiography is no longer used for diagnosis and is used only for interventional management. Echocardiography is used for risk stratification of these patients. In this article, we review the role of imaging in the evaluation of acute PE.

Advances in Interventional Pulmonology.

Much has changed since the last review of interventional pulmonology (IP) published in this Clinics series. The rate of development of new techniques and their complexities require IP physicians to be constantly maintaining and updating their skill set. International agreed training pathways help ensure that the interventionalists of the present and future have the required knowledge of anatomy, manual dexterity, and clinical judgment to keep up with the continuing advances that are constantly expanding IP's diagnostic and therapeutic boundaries. IP remains one of the most desirable subspecialities in pulmonology, and the technologic advances make the future an exciting one.

A Health Care Worker with Ebola Virus Disease and Adverse Prognostic Factors Treated in Sierra Leone.

We describe the management of a Sierra Leonean health care worker with severe Ebola virus disease complicated by diarrhea, significant electrolyte disturbances, and falciparum malaria coinfection. With additional resources and staffing, high quality care can be provided to patients with Ebola infection and adverse prognostic factors in west Africa.

How Common Is Airflow Limitation in Patients With Emphysema on CT Scan of the Chest?

BACKGROUND: COPD has traditionally been defined by the presence of irreversible airflow limitation on spirometry using either the GOLD (Global Initiative for Chronic Obstructive Lung Disease) or American Thoracic Society/European Respiratory Society criteria (lower limit of normal [LLN]). We have observed that some patients with clinical COPD and emphysema on chest CT scan have no obstruction on spirometry. The purpose of this study was to assess the prevalence of obstruction by GOLD and LLN criteria in patients with emphysema on CT scan and determine which radiographic criteria were associated with a clinical diagnosis of COPD. METHODS: We retrospectively analyzed the clinical records and spirometry of all patients who had radiographically defined emphysema on chest CT scans completed at the University of Vermont in 2011. We compared spirometric criteria and CT scan factors with the presence of clinical COPD based on chart review. RESULTS: We identified 274 patients with CT scan-defined emphysema. GOLD criteria detected obstruction in 228 patients (83%), and LLN detected obstruction in 206 patients (75%). However, GOLD failed to correctly identify 19 patients (6.9%) and LLN failed to identify 38 patients (13.9%) (average 10.4%) who had radiographic emphysema and a clinical diagnosis of COPD. Obese patients had a lower prevalence of obstruction whether classified by LLN or GOLD. Among patients with spirometric obstruction, there were greater degrees of emphysema and more severely increased airway wall thickness. Factors that were independently associated with clinical COPD were lower FVC % predicted, lower FEV1/FVC ratio, and increasing airway wall thickness. CONCLUSIONS: Spirometry missed 10.4% of patients with clinical COPD who have significant emphysema on chest CT scan.

Sniff nasal inspiratory pressure versus IC/TLC ratio as predictors of mortality in COPD.

BACKGROUND: Hyperinflation is a recognized adverse prognostic factor in COPD. As the sniff inspiratory nasal pressure (SnIP) principally reflects the severity of hyperinflation in COPD, we hypothesized that it might also be a predictor of mortality. We therefore compared the SnIP to the inspiratory capacity-to-total lung capacity (IC/TLC) ratio as predictors of mortality in advanced COPD. METHODS: A retrospective mortality analysis of 110 patients with COPD (mean FEV(1) 1.01litres, 37% predicted; 66% male) was performed. All patients had SnIP and lung volume measurements performed. The power of each test to predict mortality was determined, and predicted survival curves were created for both the SnIP and IC/TLC ratio. RESULTS: 37 patients (34%) died during the study period (29 male, 8 female). Mortality rates were analysed with a Chi(2) test; there was a significant trend towards male death (mortality rate male vs. female; 39.7% vs. 21.6% respectively; chi(2)p=0.058, Chi 3.6). ROC curves demonstrated that both SnIP and IC/TLC ratio are predictors of mortality, but analysis by Cox proportional hazards suggested the SnIP has a stronger predictive power (SnIP vs. IC/TLC ratio; p=0.017 vs 0.525; HR 0.97 vs 0.99 respectively), and analysis of the area under ROC curves (AUC) suggest that SnIP is a better discriminator than IC/TLC ratio (AUC SnIP vs IC/TLC; 0.679 vs 0.618). CONCLUSIONS: The SnIP conveys at least as much predictive power for mortality in COPD as hyperinflation determined by IC/TLC ratio. This test is cheaper, quicker and easier than measuring lung volumes by plethysmography.

Unilateral extrapulmonary airway bypass in advanced emphysema.

BACKGROUND: Gas trapping in emphysema results in resting and dynamic hyperinflation. We tested the hypothesis that a direct connection between the lung parenchyma and the atmosphere could increase expiratory flow and thereby potentially improve dyspnea through the relief of gas trapping. METHODS: Ex vivo we studied 7 emphysematous lungs and 3 fibrotic lungs (as controls) and measured expiratory flow before and after airway bypass insertion during a forced maneuver in an artificial thorax. Pilot studies were conducted in vivo in 6 patients with advanced emphysema using a size 9 endotracheal tube as a bypass surgically placed through the chest wall into the upper lobe. RESULTS: In the ex vivo emphysematous lungs the volume expelled during a forced expiratory maneuver increased from 169 to 235 mL (p < 0.05). In the in vivo group 4 patients retained the bypass tube for 3 months or more; total lung capacity was reduced, and the forced expiratory volume in 1 second increased by 23% (mean percent predicted at baseline versus 3 months, 24.4% versus 29.5%). CONCLUSIONS: An extrapulmonary airway bypass increases expiratory flow in emphysema. This may be a useful approach in hyperinflated patients with homogeneous emphysema.

Malignant mesothelioma.

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10-20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.

Physiological properties of human diaphragm muscle fibres and the effect of chronic obstructive pulmonary disease.

The contractile and actomyosin ATPase properties of single fibres were examined in human diaphragm muscle obtained from patients with and without chronic obstructive pulmonary disease (COPD). Costal diaphragm biopsies were taken from five patients without evidence of COPD and from 11 age-matched individuals with varying degrees of the disease. Our aim was to establish whether changes in contractile properties of COPD diaphragm could be fully explained by the previously documented shift towards a greater proportion of type I myosin heavy chain isoform in COPD. The relative proportion of type I diaphragm fibres from non-COPD and COPD patients was measured by gel electrophoresis, and was negatively correlated with FEV(1) over the full range of values investigated. There was also significant atrophy of the type I fibre population in COPD diaphragms. Isometric tension was similar among the fibre types and between the COPD and non-COPD patients. The intrinsic energetic properties of diaphragm fibres were examined by monitoring the time-resolved actomyosin ATPase activity in COPD and non-COPD fibres that produced similar isometric forces. The isometric ATPase rate in COPD fibres was reduced to 50% of the rate in non-COPD fibres; hence, the cost of isometric contraction in type I and type IIA COPD fibres was reduced to between one-third and one-half of the tension cost calculated for non-COPD fibres. The rate of force development in type I COPD fibres was reduced to 50% of the rate seen in non-COPD type-I fibres. No difference in the rate of ATP consumption between COPD and non-COPD fibres was evident during isovelocity shortening. These data extend previous findings showing that aspects of breathing mechanics during progressive COPD are associated with remodelling of the diaphragm fibre-type distribution; on top of the increase in type I fibres there are fibre-specific reductions in force development rate (type I fibres) and ATPase rate that are consistent with the impairment of cross-bridge cycling kinetics.

Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease.

BACKGROUND: Prognosis in chronic obstructive pulmonary disease (COPD) is poorly predicted by indices of air flow obstruction, because other factors that reflect the systemic nature of the disease also influence prognosis. OBJECTIVE: To test the hypothesis that a reduction in quadriceps maximal voluntary contraction force (QMVC) is a useful predictor of mortality in patients with COPD. METHODS: A mortality questionnaire was sent to the primary care physician of 184 patients with COPD who had undergone quadriceps strength measurement over the past 5 years. QMVC was expressed as a percentage of the patient's body mass index. The end point measured was death or lung transplantation, and median (range) follow-up was 38 (1-54) months. RESULTS: Data were obtained for 162 patients (108 men and 54 women) with a mean (SD) percentage of forced expiratory volume in 1 s (FEV1) predicted of 35.6 (16.2), giving a response rate of 88%. Transplant-free survival of the cohort was 93.5% at 1 year and 87.1% at 2 years. Cox regression models showed that the mortality risk increased with increasing age and with reducing QMVC. Only age (HR 1.72 (95% CI 1.14 to 2.6); p = 0.01) and QMVC (HR 0.91 (95% CI 0.83 to 0.99); p = 0.036) continued to be significant predictors of mortality when controlled for other variables in the multivariate analysis. CONCLUSION: QMVC is simple and provides more powerful prognostic information on COPD than that provided by age, body mass index and forced expiratory volume in 1 s.

Passive properties of the diaphragm in COPD.

Structural adaptations that occur in the diaphragm muscle of patients with chronic obstructive pulmonary disease (COPD), namely an increase in type I fibers and a decrease in type II fibers, have been explored in terms of the active contractile properties of the diaphragm. The aim of this study was to test the passive properties of the diaphragm by measuring the force response of relaxed diaphragm muscle fibers to stretching to determine the effect of COPD on these properties. Costal diaphragm biopsies were taken from patients with COPD and from controls with normal pulmonary function. From these biopsies, titin expression was assessed in diaphragm homogenates by gel electrophoresis, and the restoring force was measured by incremental stretching of single fibers in the relaxed state and measuring the force response to stretching. A quadratic model was used to illustrate the relationship between restoring force and muscle fiber length, and it revealed that COPD fibers generate significantly lower restoring forces than control fibers as judged by the area under the force-length curve. Furthermore, this finding applies to both type I and type II fibers. Gel electrophoresis revealed different titin isoforms in COPD and controls, consistent with the conclusion that COPD results not only in a change in muscle fiber-type distribution but in a structural change in the titin molecule in all muscle fiber types within the diaphragm. This may assist the muscle with the energetic changes in the length of the diaphragm required during breathing in COPD.