Is polypharmacy a risk factor for aspiration pneumonia in older adults? A case-control study.

INTRODUCTION: The incidence of aspiration pneumonia and the number of medicines prescribed increase with older age. Many medicines pose a risk for aspiration pneumonia, especially those that decrease swallowing function. Older adults with polypharmacy often receive a combination of these medicines. This study aimed to clarify whether polypharmacy is a risk factor for aspiration pneumonia. METHODS: Older adults aged ≥ 65 years receiving oral medicines were included in this case-control study. Patients hospitalized for pneumonia served as the case group, and other age-matched hospitalized patients served as the control group. Patient data were collected retrospectively, and logistic regression analysis was performed using items that showed significant differences in the univariate analysis as explanatory variables. RESULTS: Logistic regression analysis revealed that the number of medicines was not a risk factor for aspiration pneumonia; however, it was associated with the Functional Oral Intake Scale score, male sex, body mass index, and number of comorbidities. CONCLUSION: Although polypharmacy is often defined only by the number of medicines, it is not a risk factor for aspiration pneumonia. A detailed comparison of prescription medicines between the pneumonia and non-pneumonia groups is necessary.

Rhabdomyolysis Complicated with Hyponatremia Due to Water Intoxication and Severe Aspiration Pneumonia: Description of a Patient with Chronic Schizophrenia and Literature Review.

Hyponatremia due to water intoxication is frequently observed in patients with chronic schizophrenia. We herein present a 49-year-old man who developed schizophrenia at the age of 23 and had been admitted to the closed ward of our hospital for 7 years. He was found by a round nurse standing at the bedside, covering both ears with his hands and making groaning noises. He was disoriented and immediately after being returned to bed, a general tonic-clonic seizure occurred. Severe hyponatremia (Na 104 mEq/L) was noted and intravenous sodium correction was started. A few hours later, due to glossoptosis and massive vomiting, ventilation got worse to the point where he had to be put on a ventilator. On the following day, he developed aspiration pneumonia and antimicrobial treatment was started. In addition, a blood sample taken 36 hours later revealed an extensive elevation of creatine kinase (41,286 U/L), pointing to a possibility of rhabdomyolysis as a complication. Subsequently, the general condition gradually improved with antimicrobial therapy and sodium correction. He eventually recovered without any complications including central pontine myelinolysis. He had no history of polydipsia before this event but it was later found that esophageal stricture triggered complusive fluid intake, resulting in acute hyponatremia, seizure, aspiration pneumonia and rhabdomyolysis. A brief discussion will be provided on the issues surrounding hyponatremia, rhabdomyolysis and schizophrenia.

Effects of Fasting versus Non-Fasting on Emetic Complications in Radiological Examinations Using Intravascular Non-Ionic Iodinated Contrast Media: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the incidence of aspiration pneumonia, nausea, and vomiting after intravascular administration of non-ionic iodinated contrast media (ICM) between patients who fasted before contrast injection and those who did not. MATERIALS AND METHODS: Ovid-MEDLINE and Embase databases were searched from their inception dates until September 2022 to identify original articles that met the following criteria: 1) randomized controlled trials or observational studies, 2) separate reports of the incidence of aspiration pneumonia, nausea, and vomiting after intravascular injection of non-ionic ICM, and 3) inclusion of patients undergoing radiological examinations without fasting. A bivariate beta-binomial model was used to compare the risk difference in adverse events between fasting and non-fasting groups. The I² statistic was used to assess heterogeneity across the studies. RESULTS: Ten studies, encompassing 308013 patients (non-fasting, 158442), were included in this meta-analysis. No cases of aspiration pneumonia were reported. The pooled incidence of nausea was 4.6% (95% confidence interval [CI]: 1.4%, 7.8%) in the fasting group and 4.6% (95% CI: 1.1%, 8.1%) in the non-fasting group. The pooled incidence of vomiting was 2.1% (95% CI: 0.0%, 4.2%) in the fasting group and 2.5% (95% CI: 0.7%, 4.2%) in the non-fasting group. The risk difference (incidence in the non-fasting group-incidence in the fasting group) in the incidence of nausea and vomiting was 0.0% (95% CI: -4.7%, 4.7%) and 0.4% (95% CI: -2.3%, 3.1%), respectively. Heterogeneity between the studies was low (I² = 0%-13.5%). CONCLUSION: Lack of fasting before intravascular administration of non-ionic ICM for radiological examinations did not increase the risk of emetic complications significantly. This finding suggests that hospitals can relax fasting policies without compromising patient safety.

Swallowing study using water-soluble contrast agents may increase aspiration sensitivity and antedate oral feeding without respiratory and drug complications: A STROBE-compliant prospective, observational, case-control trial.

Although the modified barium swallowing study (MBSS) is considered the gold standard for assessing aspiration risk, aspiration of lipid-soluble barium can cause chemical pneumonitis or impair radiologic interpretation of the lungs. Water-soluble contrast agents (WSCAs) may avoid these complications while maintaining sensitivity on aspiration. This prospective, observational, case-control cohort trial evaluated all patients >3 years old referred for swallowing study from September 2015 to November 2017. Repeat evaluations of individuals were excluded. High-risk patients were evaluated by WSCA (iohexol)-based swallowing study (WSS) and others by MBSS. The study included 829 evaluations of 762 patients. After excluding 74 evaluations, 365 WSSs and 390 MBSSs were performed. The most frequent underlying condition was brain lesion, followed by aspiration pneumonia. Aspiration occurred more frequently in WSS (147 patients: 40.3%) than in MBSS (36 patients: 9.2%) (P = .00). However, neither aspiration volume (6.72 cc [3.09-10.35] vs 5.53 cc [2.21-8.85]) nor radiographic alterations differed between the 2 groups (P > .05). Moreover, the swallowed (16.62 cc [8.45-24.79]) and aspirated amounts of iohexol were not correlated with radiologic changes or deterioration (P > .05). Switching to oral feeding following WSS was more frequent (164 patients: 44.9%), whereas aspiration pneumonia was not (P = .00). WSS did not prolong the interval to patient discharge (P = .06) or induce an allergic reaction or chemotoxicity over 1 week. The absence of aspiration-induced complications and adverse drug effects suggests that, compared with MBSS, WSS may increase aspiration sensitivity and early switching to oral feeding.

Outcomes of elderly patients with organophosphate intoxication.

This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (P < 0.001), shock (P < 0.001) and kidney injury (P = 0.001) than survivors did. Kaplan-Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test, P < 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045-166.667, P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.

Exploring a Safety Signal of Antipsychotic-Associated Pneumonia: A Pharmacovigilance-Pharmacodynamic Study.

An association between antipsychotic drugs and pneumonia has been demonstrated in several studies; however, the risk for pneumonia caused by specific antipsychotics has not been extensively studied. The underlying mechanism is still unknown, and several receptor mechanisms have been proposed. Therefore, using a combined pharmacovigilance-pharmacodynamic approach, we aimed to investigate safety signals of US Food and Drug Administration (FDA)-approved antipsychotics for reporting pneumonia and the potential receptor mechanisms involved. A disproportionality analysis was performed to detect a signal for reporting "infective-pneumonia" and "pneumonia-aspiration" and antipsychotics using reports submitted between 2004 and 2019 to the FDA adverse events spontaneous reporting system (FAERS) database. Disproportionality was estimated using the crude and the adjusted reporting odds ratio (aROR) and its 95% confidence interval (CI) in a multivariable logistic regression. Linear regressions investigated the relationship between aROR and receptor occupancy, which was estimated using in vitro receptor-binding profiles. Safety signals for reporting infective-pneumonia were identified for clozapine (LL = 95% 3.4, n = 546 [aROR: 4.8]) as well as olanzapine (LL = 95% 1.5, n = 250 [aROR: 2.1]) compared with haloperidol, while aRORs were associated with higher occupancies of muscarinic receptors (beta = .125, P-value = .016), yet other anti-muscarinic drugs were not included as potential confounders. No safety signals for reporting pneumonia-aspiration were detected for individual antipsychotics. Multiple antipsychotic use was associated with both reporting infective-pneumonia (LL 95%: 1.1, n = 369 [aROR:1.2]) and pneumonia-aspiration (LL 95%: 1.7, n = 194 [aROR: 2.0]). Considering the limitations of disproportionality analysis, further pharmacovigilance data and clinical causality assessment are needed to validate this safety signal.

[Aspiration pneumonia after ingestion of kerosene - lamp oil is not a remedy]. / Aspirationspneumonie nach Petroleumingestion ­ Lampenöl ist kein Heilmittel.

HISTORY: We present the case of a 78-year old man, who developed aspiration pneumonia and consecutive sepsis after ingestion of a small amount of kerosene. FINDINGS AND DIAGNOSIS: Because unintentional ingestion was suspected first, diagnostic clarification of dementia was requested. Extensive exploration of the patient and third-party anamnesis excluded a psychiatric illness. Instead, a strong belief in alternative medical promises of healing was revealed as the true cause. THERAPY AND COURSE: Thus, psychiatric treatment was not neccessary, while physical condition improved after administration of antimicrobial substances. CONCLUSIONS: Psychiatric consultation may be helpful to diagnostically contextualize behaviour suggesting a mental illness.

Pathological responses to low-dose irradiation and Pepleomycin in Oral squamous cell carcinoma are predictive of Locoregional control.

BACKGROUND: The prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important. Therefore, risk-adapted treatment regimens need to be designed. We herein investigated whether pathological responses in oral cancer patients treated with preoperative chemoradiotherapy predict locoregional recurrence. METHODS: We retrospectively reviewed the data of 51 oral cancer patients who received preoperative radiotherapy and concurrent pepleomycin, followed by curative surgery at our institution between January 2009 and June 2018. Each patient received preoperative external beam irradiation to the primary tumor and lymphatics (2 Gy per day for approximately 3 weeks) concurrent with pepleomycin (2.5 mg/day). Surgery was performed approximately 3-4 weeks after the completion of preoperative chemoradiotherapy. Pathological responses were defined based on the grading system of Oboshi and Shimosato. RESULTS: Eight, 22, 16, and 5 patients had Oboshi and Shimosato grades 2a, 2b, 3, and 4, respectively. Favorable pathological responses (grades 3 and 4) were observed in 41.2% of patients (21 out of 51 patients). The pathological response and number of pathological lymph node metastases were identified as significant prognostic factors for locoregional control in the univariate analysis. Three-year locoregional control rates were 100 and 56.6% in patients with favorable and unfavorable pathological responses, respectively. CONCLUSIONS: The present study demonstrated that pathological tumor responses to preoperative chemoradiotherapy are a useful predictive factor for locoregional control.

Cytotoxic effects of dental prosthesis grinding dust on RAW264.7 cells.

Respiratory diseases, including pulmonary fibrosis, silicosis, and allergic pneumonia, can be caused by long-term exposure to dental prosthesis grinding dust. The extent of the toxicity and pathogenicity of exposure to PMMA dust, Vitallium dust, and dentin porcelain dust differs. The dust from grinding dental prosthesis made of these three materials was characterized in terms of morphology, particle size, and elemental composition. The adverse effects of different concentrations of grinding dust (50, 150, 300, 450, and 600 µg ml-l) on RAW264.7 macrophages were evaluated, including changes in cell morphology and the production of lactate dehydrogenase (LDH) and reactive oxygen species (ROS). The dust particles released by grinding dental prosthesis made of these materials had different morphologies, particle sizes, and elemental compositions. They also induced varying degrees of cytotoxicity in RAW264.7 macrophages. A possible cytotoxicity mechanism is the induction of lipid peroxidation and plasma membrane damage as the dust particles penetrate cells. Therefore, clinicians who regularly work with these materials should wear the appropriate personal protection equipment to minimize exposure and reduce the health risks caused by these particulates.

Risk factors for aspiration pneumonia during concurrent chemoradiotherapy or bio-radiotherapy for head and neck cancer.

BACKGROUND: Aspiration pneumonia is one of the most important side effects of chemoradiotherapy (CRT) and bio-radiotherapy (BRT) in patients with head and neck cancer (HNC). Aspiration pneumonia can lead to cancer-related mortality in HNC patients. However, the relationship between aspiration pneumonia occurring during CRT or BRT for HNC and treatment outcomes in HNC patients is not well characterized. In this study, we assessed the influence of aspiration pneumonia on treatment outcomes and sought to identify the clinical risk factors for aspiration pneumonia during definitive CRT and BRT in HNC patients. METHODS: We retrospectively assessed the data pertaining to patients with locally advanced HNC who received definitive CRT or BRT at the Shizuoka Cancer Center between August 2006 and December 2016. RESULTS: Among the 374 HNC patients who received CRT or BRT, 95 (25.4%) developed aspiration pneumonia during treatment. Aspiration pneumonia was significantly associated with therapeutic response to CRT or BRT (multivariate adjusted odds ratio for complete response, 0.52, p = 0.020) and poor overall survival (multivariate adjusted hazard ratio for overall survival, 1.58, p = 0.024). The multivariate analyses identified four independent factors for aspiration pneumonia: poor oral hygiene, high N-classification, hypoalbuminemia before treatment, and inpatient treatment. CONCLUSIONS: Aspiration pneumonia occurring during CRT or BRT has a detrimental effect on the therapeutic response and survival of HNC patients. Careful attention should be paid to these risk factors for aspiration pneumonia in HNC patients undergoing CRT or BRT.

Critical role of mitochondrial oxidative stress in acid aspiration induced ALI in mice.

Acute lung injury (ALI) is a pulmonary inflammatory disorder which causes significant mortality in critically ill patients. Intracellular oxidative stress has been considered to be the major component in the pathogenesis of ALI but exact source of intracellular ROS is not clearly known. The present study has been designed to elucidate the role of NADPH oxidase system and/or mitochondrial oxidative stress and its downstream pathway NLRP3 inflammasomes in mouse model of acid aspiration mediated ALI. Our data showed that acid aspiration induced lung inflammation was associated with enhanced oxidative stress as evident by data on MDA levels, nitrite levels and redox imbalance. Further acid aspiration resulted in elevation of expression of NADPH oxidase subunits (gp91 phox/p22 phox/p67 phox) as well as mitochondrial oxidative stress as reflected by aconitase activity, mitochondrial ROS levels. Interestingly, NADPH oxidase inhibitor, apocynin did not alter lung inflammation upon HCl instillation. Conversely, mitochondrial antioxidant mito-tempo resulted in significant amelioration of lung inflammation as indicated by suppression of pulmonary neutrophils and inflammatory cytokines namely IL-1ß, TNF-α, IL-6 in BALF. Analysis of mitochondrial enzymes aconitase/mitochondrial ROS/Mn-SOD confirmed that reduction in lung inflammation by mito-tempo was associated with normalization of oxidative stress in mitochondria. Further, mito-tempo administration blunted phosphorylation of p65- NF-κB at Ser 536. Finally, mito-tempo downregulated HCl-induced NF-κB-dependent pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6) drastically at mRNA levels. Overall, our data support that mitochondrial oxidative stress is crucial in modulating the HCl induced lung inflammation and identifies mitochondrial-targeted antioxidant as a potential therapeutic agent.

The effects of barium concentration levels on the pulmonary inflammatory response in a rat model of aspiration.

PURPOSE: Barium sulfate (Ba) suspension is the most widely used contrast agent for upper gastrointestinal and videofluoroscopic swallow studies (VFSS). The effect of Ba concentration on lung injury is uncertain. The aims of this study were to explore the effects of different barium concentrations on the respiratory organs and elucidate the underlying mechanisms of these effects in an established animal model of aspiration. METHODS: Animal model study. Eight-week-old male Sprague-Dawley rats were allocated into three groups (n = 12, each group). Two groups underwent tracheal instillation of low (30% w/v) and high (60% w/v) concentration Ba (low-Ba, high-Ba). A control group was instilled with saline. Half of the animals were euthanized on day 2 and the remaining half were euthanized on day 30. Histological and gene analyses were performed. RESULTS: Both low-Ba and high-Ba aspiration caused inflammatory cell infiltration in the lung at 2 days post aspiration with an increase in the expression of inflammatory cytokines. At 30 days post aspiration, small quantities of barium particles remained in the lung of the low-Ba group without any inflammatory reaction. Chronic inflammation was recognized in the high-Ba group up to 30 days post aspiration. CONCLUSION: A small amount of high concentration Ba (60% w/v) caused sustained inflammation in the rat lung at least 30 days after aspiration. Even with a small amount of low concentration Ba aspiration (30% w/v), Ba particles can remain in the lung over a month, causing sustained late effects.

Association between dipeptidyl peptidase-4 inhibitor and aspiration pneumonia: disproportionality analysis using the spontaneous reporting system in Japan.

PURPOSE: Dipeptidyl peptidase-4 inhibitor (DPP-4-Is), a kind of drug used for the treatment of diabetes, is considered to prevent the degradation of substance P that suppresses the occurrence of dysphagia. On the other hand, DPP-4 inhibitors are also known to act on the immune system. In this study, we used a spontaneous reporting system to evaluate the signals for dysphagia and aspiration pneumonia with DPP-4-Is. METHODS: We calculated reporting odds ratio (ROR) and information coefficients (IC) as disproportionality analysis to evaluate DPP-4-Is induced dysphagia and aspiration pneumonia using the Japanese Adverse Drug Event Report (JADER) database. RESULTS: For DPP-4-Is as a class, no signals were detected for dysphagia, but the signal for aspiration pneumonia was detected at ROR 1.67 (95% confidence interval [95% CI]: 1.20 to 2.34) and IC 0.70 (95% CI: 0.21 to 1.19). For aspiration pneumonia, trelagliptin was the only drug among the DPP-4-Is for which both ROR and IC signals were detected (ROR 9.99, 95% CI: 4.10 to 24.36; IC: 1.98, 95% CI: 0.78 to 3.18). ROR signals, but not IC signals, were detected for linagliptin (ROR 2.66, 95% CI: 1.19 to 5.94; IC: 1.09, 95% CI: - 0.004 to 2.19) and sitagliptin (ROR 1.84, 95% CI: 1.04 to 3.25; IC: 0.78, 95% CI: - 0.03 to 1.58). CONCLUSION: Since DPP-4 inhibitors prevent the degradation of substance P involved in swallowing reflex, DPP-4 inhibitors were expected to prevent dysphagia and aspiration pneumonia. However, this study revealed that DPP-4 inhibitors strongly were associated with onset rather than preventing aspiration pneumonia. This result suggests that DPP-4 inhibitors may affect the immune function associated with the development of aspiration pneumonia. Furthermore, there is a possibility that the amount of DPP-4-Is used clinically cannot increase the amount of substance P in sufficient quantity to prevent aspiration pneumonia.

Liquid Mosquito Repellent Ingestion in Children.

OBJECTIVES: Hydrocarbons are a common cause of accidental poisoning in children, with kerosene being the most implicated agent in rural parts of India. However, lately, liquid mosquito repellent ingestion is emerging as an important cause of hydrocarbon (kerosene) poisoning in urban households. METHODS: This is a retrospective case series over a 5-y period (January 2013 - December 2017) of children with accidental liquid mosquito repellent ingestion presenting to the pediatric emergency. Epidemiology, clinical profile, management and outcomes are discussed. RESULTS: Twenty-three children with median (IQR) age of 24 (18.8-32) mo presented after mean (SD) interval of 6 (3) h from ingestion. Majority (20, 87%) were seen during summer months (March-June) and all were from urban background. Sixteen (70%) had mild-moderate acute respiratory distress syndrome (ARDS) requiring supplemental oxygen with or without positive airway pressure for a mean (SD) duration of 3.3 (1.9) d. All except one survived. CONCLUSIONS: Children with accidental liquid mosquito repellent ingestion had predominant aspiration pneumonitis due to hydrocarbon content rather than neurological complications attributable to synthetic pyrethroids. Ensuring child-proof containers, appropriate storage, regulatory surveillance and parental awareness are must for prevention.

Pneumonia in a Teenager Hiding a Fire-Eating Stunt.

Pneumonia in children due to hydrocarbon aspiration is usually the result of an uncommon accidental event. However, an acute and severe type of pneumonia induced by hydrocarbon aspiration is occasionally experienced by entertainers known as fire-eaters. Different approaches to treat fire-eater's pneumonia appear in the literature. Although there is no consensus regarding the management of this condition, the use of antibiotic therapy is well recognized and recommended by some, whereas others recommend only supportive treatment. Steroids are indicated in severe cases.Here, we report the case of a boy who developed severe pneumonia after inhaling hydrocarbons during an attempt to mimic a fire-eater show. Slow resolution was achieved after broad-spectrum antibiotic therapy in addition to systemic and inhaled steroids and physiotherapy.