Jiro Ito

Enteral Nutrition Is a Risk Factor for Airway Complications in Subjects Undergoing Noninvasive Ventilation for Acute Respiratory Failure

BACKGROUND: Early enteral nutrition is recommended for mechanically ventilated patients in several studies and guidelines. In contrast, the effects of early enteral nutrition on noninvasive ventilation (NIV) have not been investigated extensively. The lack of an established method of airway protection suggests that enteral nutrition administration to these patients could increase airway complications and worsen outcomes. METHODS: Between January 2007 and January 2015, 150 patients were admitted to our respiratory department for acute respiratory failure and received NIV for >48 h. Of these, 107 subjects incapable of oral intake were retrospectively analyzed. Clinical background and complications were compared in subjects who did and did not receive enteral nutrition. RESULTS: Sixty of the 107 subjects (56%) incapable of oral intake who received NIV also received enteral nutrition. Serum albumin concentration was significantly lower in subjects who received enteral nutrition than in those who did not (mean 2.7 ± 0.68 mg/dL vs 3.0 ± 0.75 mg/dL, P = .048). The rate of airway complications was significantly higher (53% [32/60] vs 32% [15/47], P = .03), and median NIV duration was significantly longer (16 [interquartile range 7–43] d vs 8 [5–20] d, P = .02) in subjects who received enteral nutrition than in those who did not. Multivariate analysis showed that enteral nutrition was unrelated to in-hospital mortality. CONCLUSIONS: Among subjects receiving NIV, enteral nutrition was associated with increased risk of airway complications but did not affect mortality. Enteral nutrition should be carefully considered in these patients.

Aprepitant for refractory nivolumab-induced pruritus

Although substantial progress has been made in the treatment of non-small-cell lung cancer (NSCLC) patients with immune checkpoint inhibitors (ICIs), severe immune-related adverse events (irAEs) sometimes occur. Here, we report a case of severe refractory pruritus after Stevens-Johnson syndrome (SJS) in a patient with NSCLC treated with nivolumab. The patient was a 76-year-old Japanese woman with advanced NSCLC treated with nivolumab. After the second dose, she experienced severe rash with mucous involvement. We diagnosed SJS and started 50mg of oral prednisolone (1mg/kg). The rash completely resolved after prednisolone was started, but we could not manage the severe pruritus with emollients, antihistamines, and steroids. Finally, we administered aprepitant, an oral neurokinin-1 receptor antagonist, for her refractory pruritus. Her symptoms improved within 5days. Severe refractory pruritus can arise from ICIs, and aprepitant may be a useful treatment.

A pilot trial of nivolumab treatment for advanced non-small cell lung cancer patients with mild idiopathic interstitial pneumonia

INTRODUCTION Nivolumab has demonstrated efficacy against metastatic non-small cell lung cancer (NSCLC). However, immune-related adverse events can occur, among which pneumonitis is relatively common. Lung cancer patients with idiopathic interstitial pneumonia (IIP) have a higher risk of pneumonitis associated with anticancer therapy. We hypothesized that the benefit of nivolumab may outweigh the risks of pneumonitis in patients with NSCLC who have mild IIP. We performed a pilot trial to evaluate the safety of nivolumab in NSCLC patients with mild IIP. METHODS Previously treated, inoperable NSCLC patients with mild IIP were enrolled. Mild IIP was defined as having a predicted vital capacity ≥80% and a possible usual interstitial pneumonia (UIP) or inconsistent with UIP pattern on chest high-resolution computed tomography. Patients received nivolumab at a dose of 3mg/kg biweekly. RESULTS Six patients were enrolled in this trial between April 2016 and December 2016. None experienced drug-related nonhematologic grade 3/4 or hematologic grade 4 adverse events in the 12 weeks following the initiation of nivolumab treatment. Furthermore, none of the patients had pneumonitis of any grade. At the time of analysis, all patients were alive, and 3 had experienced a partial response. CONCLUSIONS Nivolumab therapy may be feasible in NSCLC patients with mild IIP. (Trial registration number: UMIN000022037).

Characteristics and Prognostic Impact of Pneumonitis during Systemic Anti-Cancer Therapy in Patients with Advanced Non-Small-Cell Lung Cancer

Background Data on characteristics, outcomes, and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who develop pneumonitis during systemic anti-cancer therapy (pneumonitis) are currently lacking. Methods We conducted a retrospective cohort study of 910 consecutive patients diagnosed with advanced NSCLC between January 2004 and January 2014. Of these, 140 patients were excluded because they did not receive systemic anti-cancer therapy at this hospital. Results A total of 770 patients were included in the study, of whom 44 (6%) were diagnosed with pneumonitis. The mortality rate of pneumonitis was 36%. The incidence of pneumonitis was independently associated with pre-existing ILD (adjusted odds ratio, 2.99, P = 0.008), and survivors were significantly associated with younger age (P = 0.003) and radiographic non-acute interstitial pneumonia pattern (P = 0.004). In all patients, pneumonitis was identified as an independent predictor of overall survival (OS) (adjusted hazard ratio 1.53, 95% CI, 1.09–2.09, P = 0.015). Performance status was poor in 82% of survivors of pneumonitis; in 62% of survivors, the PS worsened after the pneumonitis improved. Additionally, 54% of survivors received no further systemic anti-cancer therapy after pneumonitis. The median survival time of survivors after pneumonitis was 3.5 months (95% CI, 2.3–7.2 months). Conclusions Our study indicated that 6% of patients with advanced NSCLC developed pneumonitis during systemic anti-cancer therapy. The early mortality rate of pneumonitis is high, and the survival and PS after pneumonitis is extremely poor. Additionally, pneumonitis has an adverse impact on the survival of patients with advanced NSCLC. These data should be considered for the management of pneumonitis, and we recommend that future work focuses on pneumonitis particularly to improve the survival of patients with advanced NSCLC.

Analysis of advanced lung cancer patients diagnosed following emergency admission

Data on prognosis and predictors of overall survival in advanced lung cancer patients diagnosed following emergency admission (DFEA) are currently lacking. We retrospectively analysed data from 771 patients with advanced nonsmall cell lung cancer between April 2004 and April 2012. Of the 771 patients, 103 (13%) were DFEA. DFEA was not an independent predictor of overall survival by multivariate Cox proportional hazard models, whereas good performance status (PS), epidermal growth factor receptor gene mutation, stage IIIB, adenocarcinoma and chemotherapy were independent predictors of overall survival (hazard ratio (95% CI) 0.36 (0.29–0.44), p<0.001; 0.49 (0.38–0.63), p<0.001; 0.64 (0.51–0.80), p<0.001; 0.81 (0.67–0.99), p=0.044; and 0.40 (0.31–0.52), p<0.001, respectively). Good PS just prior to opting for chemotherapy, but not at emergency admission, was a good independent predictor of overall survival in DFEA patients (hazard ratio (95% CI) 0.26 (0.12–0.55); p<0.001). DFEA is relatively common. DFEA and PS at emergency admission were not independent predictors of overall survival, but good PS just prior to opting for chemotherapy was an independent predictor of longer overall survival. Efforts to improve patient PS after admission should be considered vital in such circumstances. Efforts to improve performance status after admission are vital in patients diagnosed following emergency admission http://ow.ly/C3BDQ

The clinical practice of high-flow nasal cannula oxygen therapy in adults: A Japanese cross-sectional multicenter survey

BACKGROUND High-flow nasal cannula oxygen therapy (HFNC) is widely used mainly in the acute care setting, but limited data are available on real-world practice in adults. The objective of this study was to describe HFNC practices in Japanese adults. METHODS A retrospective cross-sectional multicenter survey of adult patients receiving HFNC from January through March 2015 was conducted in 33 participating hospitals in Japan. RESULTS We obtained information on 321 patients (median age, 76; 218 men, 103 women; median estimated PaO2/FIO2, 178 mm Hg) from 22 hospitals. Do-not-intubate status was determined in 37.4% of patients. Prior to HFNC, 57.9% of patients received conventional oxygen therapy; 25.9%, noninvasive ventilation; and 15.0%, invasive mechanical ventilation. The common indications for HFNC were acute hypoxemic respiratory failure (ARF) (65.4%), postoperative respiratory support (15.9%), and post-extubation respiratory support (11.2%). The underlying etiology of ARF included interstitial lung disease, pneumonia, and cardiogenic pulmonary edema. HFNC was administered mostly in intensive care units or intermittent care units (60.7%) and general wards (36.1%). Median duration of HFNC was 4 days; median total flow rate, 40 L/min; and median FIO2, 50%. HFNC significantly improved PaO2, PaCO2, SpO2 and respiratory rate from baseline. Two-thirds of patients finally survived to be discharged or transferred. CONCLUSIONS We documented patient demographics, clinical indications, and settings of HFNC use in the real world. We also demonstrated positive effects of HFNC on respiratory parameters. Further studies are urgently needed regarding the efficacy and safety of HFNC in populations outside of previous clinical trials.

What is the Impact of Mildly Altered Consciousness on Acute Hypoxemic Respiratory Failure with Non-invasive ventilation?

Objective A severely altered level of consciousness (ALC) is considered to be a possible contraindication to non-invasive ventilation (NIV). We investigated the association between mild ALC and NIV failure in patients with hypoxemic respiratory failure. Methods A retrospective study was conducted by reviewing the medical charts of patients with de novo hypoxemic respiratory failure who received NIV treatment. The clinical background and the outcomes of patients with and without ALC were compared. Patients Patients who were admitted to our hospital for acute hypoxemic respiratory failure between July 2011 and May 2015 were included in the present study. Results Sixty-six of the 148 patients had ALC. In comparison to the patients without ALC, the patients with ALC were older (median: 72 vs. 78 years, p=0.02), had a higher Acute Physiology and Chronic Health Evaluation II score (18 vs. 19, p=0.02), and received a higher level of inspiratory pressure (8 cmH2O vs. 8, p<0.01). The median Glasgow Coma Scale score of the patients with ALC was 14 (interquartile range, 11-14). There were no significant differences between the groups in the rates of NIV failure (24% vs. 30%, p=0.4) and in-hospital mortality (13% vs. 16%, p=0.3). Conclusion NIV may be successfully applied to treat acute hypoxemic respiratory failure with mild ALC. NIV may be performed, with careful attention to the appropriate timing for intubation.

Enteral Nutrition During Noninvasive Ventilation: We Should Go Deeper in the Investigation—Reply

In reply: We thank Stefano Bambi and colleagues for highlighting these common concerns regarding the introduction of enteral nutrition during noninvasive ventilation (NIV) for acute respiratory failure. In our protocol, we use a nasogastric tube 8–12 French in diameter. Nasogastric tubes were