A real-world study of Afatinib plus ramucirumab in treatment-naïve, EGFR-mutated, non-small cell lung cancer.

BACKGROUND: Recent reports suggested combining ramucirumab with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to overcome EGFR resistance in non-small cell lung cancer (NSCLC). Nonetheless, evidence supporting the activity of afatinib and ramucirumab is lacking. This study investigated the survival benefits and safety profile of afatinib plus ramucirumab in patients with treatment-naïve, EGFR-mutated, metastatic NSCLC. MATERIALS AND METHODS: The medical records of patients with EGFR-mutated NSCLC were retrospectively retrieved. Patients who received first-line sequential afatinib followed by ramucirumab and the first-line combination of afatinib plus ramucirumab were included. The Kaplan-Meier was used to estimate the progression-free survival (PFS) of all included patients, patients on sequential afatinib followed by ramucirumab (PFS1), and patients on the up-front combination of afatinib and ramucirumab (PFS2). RESULTS: Thirty-three patients were included (25 women; median age: 63 [45-82] years). The median follow-up of the included patients was 17 months (range 6-89 months). the median PFS for the whole cohort was 71 months (95% CI 67.2-74.8) with eight events during the follow-up. The median PFS1 and PFS2 were 71 months (95 CI not defined) and 26 months (95% CI 18.6-33.4), respectively. In terms of OS, the median OS for all patients and patients on sequential treatment was not defined, while the median OS for patients on upfront combination was 30 months (95% CI 20.9-39.1). There was no significant association between EGFR mutation type and PFS1 or PFS2. CONCLUSIONS: Afatinib plus ramucirumab could improve the PFS of patients with EGFR-positive NSCLC at a predictable safety profile. Our data also suggest a survival benefit of adding ramucirumab to afatinib in patients with uncommon mutations, which should be investigated further.

Co-existing obstructive sleep apnea reduces Nuss surgery efficacy in pectus excavatum.

Nuss surgery is effective in correcting pectus excavatum (PE), with a recurrence rate of 1.2-27%. Re-do surgery is successful but still has a 6% failure rate. Patients with obstructive sleep apnea (OSA) experience repetitive PE-associated sternal depression during sleep. As the prevalence of OSA among PE patients is higher than the average, co-existing OSA in PE patients might negatively affect the efficacy of Nuss surgery. This study aimed to evaluate the impact of co-existing OSA on Nuss surgery in patients with PE. In total, 20 adult patients with PE only and 9 patients with PE and OSA were analyzed. Polysomnography was performed before Nuss surgery to evaluate OSA. Sternovertebral distance (SVD) and radiographic Haller index (RHI) were recorded before surgery and at 3, 6, and 24 months postoperatively. The results showed that percentage changes in SVD in patients with PE only at 3, 6, and 24 months postoperatively were significantly increased compared with those in the patients with PE and OSA (31.1% vs. 14.1% at 3 months; 37.5% vs. 21.4% at 6 months; 42.5% vs. 19.2% at 24 months). Meanwhile, percentage changes in RHI were significantly lower in patients with PE alone than in the patients with PE and OSA (-22.9% vs. -9.3% at 3 months; -27.9% vs. -18.7% at 6 months; -30.6% vs. -16.7% at 24 months). This study showed that co-existing OSA might reduce the efficacy of Nuss surgery for patients with PE. We recommend that patients with PE should be evaluated and treated for OSA before surgery to prevent surgical failure after bar removal.

Mucoid impaction mimicking multiple metastatic lung cancer.

The most common etiology of multiple pulmonary nodules is metastatic lung cancer. Although benign etiologies have been reported, mucoid impaction less commonly presents as multiple pulmonary nodules. Herein, we report the case of an 81-year-old demented man who presented with multiple pulmonary nodules due to mucoid impaction. Chest radiographs revealed rapid resolution after tracheostomy and adequate mucus clearance. We suggest that mucoid impaction may present as multiple pulmonary nodules mimicking multiple metastatic lung cancer.

Associations between occupational inhalation risks and FeNO levels in airway obstruction patients: results from the National Health and Nutrition Examination Survey, 2007-2012.

PURPOSE: To investigate associations between occupational inhalation risks and fractional exhaled nitric oxide (FeNO) levels in patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Data of 16,486 subjects who had undergone spirometry with pre-bronchodilator and post-bronchodilator lung function assessment were retrieved from the National Health and Nutrition Examination Survey, 2007-2012 database. After excluding 2,638 subjects with missing spirometry values, data of 13,336 subjects were included for analysis. Factors associated with occupational inhalation, FeNO levels and COPD were analyzed using logistic regression analysis. RESULTS: COPD was associated with occupational exposures to mineral dusts, organic dusts, exhaust fumes, other fumes, and second-hand smoking (P<0.05). Long-term exposure to these occupational hazards carried significantly higher risk for subjects with COPD than for controls (crude odds ratios [ORs]: mineral dusts: 2.364, organic dusts: 2.427, exhaust fumes: 2.728, other fumes: 2.144). In subgroup analysis, COPD correlated positively with long-term exposures to organic dusts and exhaust fumes in subjects with FeNO ≤50 ppb (ORs 1.361 and 1.314, respectively); conversely, COPD correlated negatively with intermediate to long-term exposures to organic dusts and exhaust fumes in those with FeNO >50 ppb (ORs 0.058 and 0.210, respectively). CONCLUSION: Occupational exposures to airborne pollutants carries higher risk of COPD than non-exposure and the risk is higher the longer the duration of exposure. Exposure-response relationships are inconsistent in subjects with suspected asthmatic airway inflammation (FeNO ≥50 ppb). More careful risk assessment is needed in occupational inhalation exposure, since COPD with asthmatic airway inflammation, or asthma-COPD overlapping syndrome, may have the distinguishing features of both COPD and asthma.

Generalized Convulsion Complicating Acute Diffuse Pulmonary Hemorrhage: The Report of a Rare Case.

PURPOSE: The immediate complications associated with a generalized tonic-clonic (GTC) seizure usually involve injuries such as aspiration pneumonia, head injury, skull or vertebral fracture and orolingual biting injury. Here we present a young man who suffered from GTC that was followed by a rare complication, acute diffuse pulmonary hemorrhage, which presented with massive hemoptysis and subsequent respiratory failure. CASE REPORT: An 18-year-old boy developed a GTC convulsion that lasted for about two minutes and then regained consciousness 15 minutes later. Another GTC convulsion occurred four hours later for about two minutes. Upon admission, coughing with blood clots was noted and was initially imputed to a bite wound affecting the tongue. However, massive hemoptysis developed soon after. A chest X-ray showed diffuse consolidation of the bilateral lungs. He was transferred to the intensive care unit and was intubated immediately owing to acute respiratory failure. A further chest CT also showed extensive consolidation of the bilateral lungs, mainly in the central and posterior portions. Bronchoscopy showed diffuse tracheal and bronchial erythematous mucosa and post-hemorrhage changes. Laboratory surveys for autoimmune disease, infectious disease, tuberculosis and intoxication gave normal results. After treatment with anticonvulsants, antibiotics and corticosteroids, he was stabilized and extubated on the 5th day of hospitalization. CONCLUSION: The disease entity of acute diffuse pulmonary hemorrhage is similar to neurogenic pulmonary edema. Physicians should be aware of this extremely rare but life-threatening complication, namely seizure-related acute diffuse pulmonary hemorrhage. The patient's response to respiratory support and corticosteroid is usually quite satisfactory.

Beneficial Effects of Long-Term CPAP Treatment on Sleep Quality and Blood Pressure in Adherent Subjects With Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular diseases. Although CPAP is the first treatment choice for moderate-to-severe OSA, acceptance of and adherence to CPAP remain problematic. High CPAP adherence is generally defined as ≥4 h of use/night for ≥70% of the nights monitored. We investigated the long-term beneficial effects of CPAP on sleep quality and blood pressure in subjects with moderate-to-severe OSA according to high or low CPAP adherence. METHODS: We retrospectively analyzed 121 subjects with moderate-to-severe OSA from August 2008 to July 2012. These subjects were divided into 3 groups: (1) no CPAP treatment (n = 29), (2) low CPAP adherence (n = 28), and (3) high CPAP adherence (n = 64). All subjects were followed up for at least 1 y. The 3 groups were compared regarding anthropometric and polysomnographic variables, presence of cardiovascular comorbidities, and blood pressure at baseline and at the last follow-up. RESULTS: The no-treatment group showed significant increases in oxygen desaturation index and blood pressure. The high-adherence group showed significant improvement in daytime sleepiness, apnea-hypopnea index (AHI), oxygen desaturation index, and blood pressure. Although the AHI was also significantly decreased after CPAP treatment in the low-adherence group, blood pressure remained unchanged. CONCLUSIONS: CPAP treatment had beneficial effects on both sleep quality and blood pressure only in subjects with OSA and high CPAP adherence who used CPAP for ≥4 h/night for ≥70% of nights monitored. Subjects with low CPAP adherence received beneficial effects on AHI, but not blood pressure.

Comparison of cardiovascular co-morbidities and CPAP use in patients with positional and non-positional mild obstructive sleep apnea.

BACKGROUND: This retrospective cohort study aimed to determine if there are differences in cardiovascular co-morbidities, blood pressure (BP) and continuous positive airway pressure (CPAP) use between patients with positional-dependent and nonpositional-dependent obstructive sleep apnea (OSA). METHODS: Patients who were referred for overnight polysomnography for suspected OSA between 2007 and 2011 were screened. A total of 371 patients with OSA were included for analysis and divided into six groups according to positional-dependency and severity of OSA: positional mild (n = 52), positional moderate (n = 29), positional severe (n = 24), non-positional mild (n = 18), non-positional moderate (n = 70) and non-positional severe group (n = 178). The six groups were compared for anthropometric and polysomnographic variables, presence of cardiovascular co-morbidities, morning and evening BP and the changes between evening and morning BP, and CPAP device usage patterns. RESULTS: Demographic and anthropometric variables showed non-positional severe OSA had poor sleep quality and higher morning blood pressures. Positional mild OSA had the lowest cardiovascular co-morbidities. Overall CPAP acceptance was 45.6%. Mild OSA patients had the lowest CPAP acceptance rate (10%), followed by moderate group (37.37%) and severe group (61.88%, P < 0.001). However, the significant difference in CPAP acceptance across OSA severity disappeared when the data was stratified by positional dependency. CONCLUSIONS: This study found that positional mild OSA had less cardiovascular co-morbidities compared with subjects with positional severe OSA. Independent of posture, CPAP acceptance in patients with mild OSA was low, but CPAP compliance was similar in CPAP acceptors regardless of posture dependency of OSA. Since there are increasing evidences of greater cardiovascular risk for untreated mild OSA, improving CPAP acceptance among mild OSA patients may be clinically important regardless of posture dependency.

Factors affecting CPAP acceptance in elderly patients with obstructive sleep apnea in Taiwan.

BACKGROUND: The prevalence of obstructive sleep apnea (OSA) increases with age. Treatment often includes CPAP. CPAP adherence is correlated with disease severity and symptoms. We hypothesized that CPAP acceptance rates in elderly patients with OSA would be lower than in younger patients with OSA, and examined factors associated with CPAP acceptance. METHODS: We reviewed the charts of 315 subjects with OSA (apnea-hypopnea index ≥ 5 events/h) who were treated at our hospital from 2008 to 2011 with CPAP therapy. All underwent CPAP titration testing before CPAP prescription. Subjects were grouped by age: young (25-40 y, n = 35), middle-age (41-65 y, n = 169), and elderly (> 65 y, n = 111). Demographic variables, excessive daytime sleepiness, overnight polysomnography study variables, CPAP acceptance, and CPAP adherence were compared. Regression analysis was performed to identify factors associated with acceptance. RESULTS: The elderly subjects had less excessive daytime sleepiness and less pronounced alterations in overnight polysomnography variables than the subjects in the other groups, but had more cardiovascular comorbidities. The CPAP acceptance rate (overall 125/315, 39.7%) was significantly lower in the elderly group, compared with the younger group (31.5% vs 60%, P = .01). CPAP acceptance was associated with fewer comorbidities, higher excessive daytime sleepiness, and higher apnea-hypopnea index, but not age. CPAP adherence was not associated with age. CONCLUSIONS: CPAP acceptance is low in elderly patients in Taiwan. CPAP acceptance, instead of CPAP adherence, is the critical issue with elderly patients with OSA.

Fish fin aspiration: an unusual type of lower airway foreign body in a Chinese adult.

Foreign body aspiration into the lower airway is rare in adults, and typically occurs in individuals of advanced age or with underlying neurological or medical conditions. The most common type of lower airway foreign body is organic substances, in particular chicken or fish bones. In many patients a history of an acute choking event is not found, and symptoms are non-specific and may be attributed to other medical conditions. Herein we report the unique case of an 80-year-old Chinese woman who aspirated a fish fin that was undiagnosed for 3 years.

Factors that affect the diagnostic yield of endobronchial ultrasonography-assisted transbronchial lung biopsy.

BACKGROUND: Endobronchial ultrasound (EBUS) is a relatively noninvasive procedure used to diagnose and stage lung cancer. Although EBUS-guided transbronchial lung biopsy (TBLB) procedures for peripheral lesions have higher diagnostic yields than traditional TBLB or fluoroscopy-assisted TBLB, the diagnostic yield is not 100%, and the reasons for this are not clear. SUBJECTS AND METHODS: This retrospective study assessed what characteristics influence the diagnostic yield of EBUS-guided TBLB. EBUS was used to locate a single peripheral lung nodule or mass, and the lesion was biopsied and pathologically characterized. Parameters that were evaluated included patient demographics, lesion location, ease of tumor sampling, location of the EBUS probe relative to the lesion, pathological volume, tumor cell type, and whether physicians were under supervision. RESULTS: Thirty-nine patients received EBUS-guided TBLB, which correctly identified 76.9% of the patients as having lung cancer. For the remaining patients, subsequent surgery indicated their tumors were malignant. Univariate logistic regression modeling indicated that only the location of the probe relative to the lesion was significantly associated with diagnostic yield of EBUS-guided TBLB. When the probe was directly within the lesion, it was 8.17 times (odds ratio 8.17; 95% confidence interval 1.41, 47.22; P=.019) more likely to have a successful TBLB than when the probe was adjacent to the lesion. CONCLUSIONS: In this study, the position of the probe relative to a peripheral lung lesion was associated with the diagnostic yield of EBUS-guided TBLB. Larger prospective studies are required to further assess what influences the diagnostic yield of this technology.

Pulmonary rehabilitation improves exercise capacity and quality of life in underweight patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: An estimated 20-40% of COPD patients are underweight. We sought to confirm the physiological and psychosocial benefits of pulmonary rehabilitation programmes (PRP) in underweight compared with non-underweight patients with COPD. METHODS: Twenty-two underweight COPD patients with BMI <20 kg/m(2), and 22 non-underweight COPD patients, who were matched for FEV(1) and age, were studied. All patients had moderate-to-very severe COPD. All patients participated in 12-week, hospital-based outpatient PRP consisting of two sessions per week. Baseline and post-PRP status were evaluated by spirometry, cardiopulmonary exercise testing, ventilatory muscle strength and the St. George's Respiratory Questionnaire (SGRQ). RESULTS: At baseline, the age distribution and airflow obstruction were similar in underweight and non-underweight patients with COPD. Baseline exercise capacity, inspiratory muscle strength and SGRQ total and symptoms scores were significantly lower in the underweight patients (all P < 0.05). After the PRP, there was significant weight gain in the underweight COPD patients (mean increase 0.8 kg, P = 0.01). There were also significant improvements in peak oxygen uptake, peak workload and the SGRQ total, symptoms, activity and impact scores in both underweight and non-underweight patients with COPD (all P < 0.05). CONCLUSIONS: Underweight patients with COPD have impaired exercise capacity and health-related quality of life (HRQL). Exercise training with supplemental oxygen may result in significant weight gains and improvements in exercise capacity and HRQL. Exercise training is indicated for underweight patients with COPD.

Increased survivin mRNA in malignant pleural effusion is significantly correlated with survival.

OBJECTIVE: The sensitivity of cytologic examination of pleural effusions is variable and not predictive of prognosis. Survivin is an inhibitor of apoptosis that may be a novel diagnostic/prognostic marker of cancers. This study aimed to determine the diagnostic and prognostic value of measuring survivin mRNA levels in pleural effusions. METHODS: Eighty-eight consecutive pleural effusion samples were examined for both cytology and survivin mRNA level. The accuracy of diagnosis and the correlation between survivin mRNA level and survival in malignant pleural effusion (MPE) were determined. Pleural effusions were divided into three groups: Group I, malignancy-associated (n = 44); Group II, inflammatory (n = 27); and Group III, transudative (n = 17). RESULTS: Survivin mRNA levels in Group I (1.03 +/- 0.61, range 0-2.96) were significantly higher than those in Groups II (0.45 +/- 0.69, range 0-3.30) and III (0.08 +/- 0.22, range 0-0.71) (P < 0.001). Survivin mRNA level was significantly higher in MPE than in non-MPE. The cut-off value for survivin mRNA levels in pleural effusions was 0.074 for the diagnosis of malignancies, with sensitivity, specificity, and positive and negative predictive values of 96%, 45%, 45% and 96%, respectively. Survivin mRNA level in pleural effusions of cancer patients significantly correlated with poor survival. CONCLUSIONS: Survivin mRNA level is significantly higher in MPEs. Over-expression of survivin mRNA correlates with poor prognosis in cancer patients.

Acute respiratory distress syndrome caused by leukemic infiltration of the lung.

Respiratory distress syndrome resulting from leukemic pulmonary infiltrates is seldom diagnosed antemortem. Two 60- and 80-year-old women presented with general malaise, progressive shortness of breath, and hyperleukocytosis, which progressed to acute respiratory distress syndrome (ARDS) after admission. Acute leukemia with pulmonary infection was initially diagnosed, but subsequent examinations including open lung biopsy revealed leukemic pulmonary infiltrates without infection. In one case, the clinical condition and chest radiography improved initially after combination therapy with chemotherapy for leukemia and aggressive pulmonary support. However, new pulmonary infiltration on chest radiography and hypoxemia recurred, which was consistent with acute lysis pneumopathy. Despite aggressive treatment, both patients died due to rapidly deteriorating condition. Leukemic pulmonary involvement should be considered in acute leukemia patients with non-infectious diffusive lung infiltration, especially in acute leukemia with a high blast count.