Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia.

Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.

Influence of housing characteristics on bacterial and fungal communities in homes of asthmatic children.

Variations in home characteristics, such as moisture and occupancy, affect indoor microbial ecology as well as human exposure to microorganisms. Our objective was to determine how indoor bacterial and fungal community structure and diversity are associated with the broader home environment and its occupants. Next-generation DNA sequencing was used to describe fungal and bacterial communities in house dust sampled from 198 homes of asthmatic children in southern New England. Housing characteristics included number of people/children, level of urbanization, single/multifamily home, reported mold, reported water leaks, air conditioning (AC) use, and presence of pets. Both fungal and bacterial community structures were non-random and demonstrated species segregation (C-score, P < 0.00001). Increased microbial richness was associated with the presence of pets, water leaks, longer AC use, suburban (vs. urban) homes, and dust composition measures (P < 0.05). The most significant differences in community composition were observed for AC use and occupancy (people, children, and pets) characteristics. Occupant density measures were associated with beneficial bacterial taxa, including Lactobacillus johnsonii as measured by qPCR. A more complete knowledge of indoor microbial communities is useful for linking housing characteristics to human health outcomes. Microbial assemblies in house dust result, in part, from the building's physical and occupant characteristics.

An environmental epigenetic study of ADRB2 5'-UTR methylation and childhood asthma severity.

BACKGROUND: Beta-2 adrenergic receptor (ADRB2) is the primary target of both short- and long-acting beta-agonist asthma medications. ADRB2 5'-UTR methylation changes in blood have the potential to act as a surrogate biomarker of responsiveness to beta-agonist treatment and childhood asthma severity. OBJECTIVE: To study the association between ADRB2 5'-UTR methylation, NO (2) exposure and childhood asthma severity. METHODS: We compared ADRB2 5'-UTR methylation levels in blood between 60 children with mild asthma and 122 children with severe asthma using methylation-specific PCR. We also investigated potential joint effects between NO (2) exposure and ADRB2 5'-UTR methylation. RESULTS: We found a significant association between intermediate (OR: 4.11, 95% CI: 1.58-10.73) and high levels (OR: 7.63, 95% CI: 3.02-19.26) of ADRB2 methylation and severe childhood asthma. In addition, we found a significant association between indoor exposure to NO (2) , an air pollutant and known asthmogen, and severe asthma among children exhibiting high ADRB2 methylation (OR: 4.59, 95% CI: 1.03-20.55) but no association among children exhibiting low levels of ADRB2 methylation (OR: 0.35, 95% CI: 0.01-14.13). CONCLUSIONS AND CLINICAL RELEVANCE: These findings support the potential use of ADRB2 5'-UTR methylation as a biomarker of both asthma severity and risk for NO (2) -associated asthma exacerbations in children, and present the first evidence of an epigenetic link between an important environmental exposure and childhood asthma severity.

Effects of chlorhexidine on human taste perception.

Chlorhexidine, a bis-cationic biguanide antiseptic, greatly reduces the perceived intensity of the salty prototype sodium chloride and may prove to be an important probe of mechanisms that underlie the human salty taste quality. Chlorhexidine, which tastes bitter, also reduces quinine hydrochloride taste intensity, but neither sweet sucrose nor sour citric acid is affected. Perceptual intensity rating and quality identification were measured for human subjects before and for 30 min following treatment with 1.34 mM chlorhexidine gluconate. In one experiment, test stimuli were the taste-quality prototypes; in a second experiment, stimuli were series of sodium, halide and sulfate salts. Experiment 1 showed a single 3-min chlorhexidine treatment resulted in reductions in taste intensity that persisted for at least 30 min. Experiment 2 showed a single 2-min chlorhexidine treatment reduced perceptual intensities of halide and sulfate salts except those with divalent cations. Chlorhexidine impaired identification of the salty quality and produced a bitter quality in nonbitter salts and impaired identification of the bitter quality of quinine, but not bitter salts. The specific effect of chlorhexidine on the bitterness of quinine suggests it may bind to the same receptor as quinine. The ability of chlorhexidine to specifically disrupt saltiness of a wide range of salts is consistent with proposed peripheral transduction mechanisms for the salty quality that involve transepithelial ion transport.

A confusion matrix for the study of taste perception.

Taste stimulus identification was studied in order to more thoroughly examine human taste perception. Ten replicates of an array of 10 taste stimuli--NaCl, KCl, Na glutamate, quinine. HCl, citric acid, sucrose, aspartame, and NaCl-sucrose, acid-sucrose, and quinine-sucrose mixtures--were presented to normal subjects for identification from a list of corresponding stimulus names. Because perceptually similar substances are confused in identification tasks, the result was a taste confusion matrix. Consistency of identification for the 10 stimuli (T10) and for each stimulus pair (T2) was quantified with measures derived from information theory. Forty-two untrained subjects made an average of 57.4% correct identifications. An average T10 of 2.25 of the maximum 3.32 bits and an average T2 of 0.84 of a maximum 1.0 bit of information were transmitted. In a second experiment, 40 trained subjects performed better than 20 untrained subjects. The results suggested that the identification procedure may best be used to assess taste function following 1-2 training replicates. The patterns of taste confusion indicate that the 10 stimuli resemble one another to varying extents, yet each can be considered perceptually unique.

Fluctuating olfactory sensitivity and distorted odor perception in allergic rhinitis.

OBJECTIVE: To characterize the relationship between allergic rhinitis, the severity and duration of nasal disease, olfactory function, and self-reported olfactory symptoms, including fluctuations or distortions in odor perception. DESIGN: Assessment of olfactory function and symptoms of 90 patients with allergic rhinitis. SETTING: A clinic of a university teaching hospital and research facility. PATIENTS: Sixty patients who presented to the Taste and Smell Clinic who had positive allergy test results and 30 patients who presented to the Allergy-Immunology Clinic. The Taste and Smell Clinic patients were grouped by nasal-sinus disease status (30 without chronic rhinosinusitis or nasal polyps, 14 with chronic rhinosinusitis but without polyps, and 16 with nasal polyps). MAIN OUTCOME MEASURES: Subjective olfactory symptom questionnaire and objective olfactory function tests. RESULTS: The Allergy-Immunology Clinic patients were diagnosed as being normosmic and the Taste and Smell Clinic patients as being hyposmic or anosmic with olfactory loss that increased significantly with nasal-sinus disease severity. Comparisons with normative data confirm that olfactory scores observed in all groups were significantly lower than expected because of the aging process alone. The self-reported duration of olfactory loss increased significantly with nasal-sinus disease severity. The Taste and Smell Clinic patients without chronic rhinosinusitis or nasal polyps reported the greatest incidence of olfactory distortions and olfactory loss associated with upper respiratory tract infections. CONCLUSIONS: There appears to be a continuum of duration and severity of olfactory loss in allergic rhinitis that parallels increasing severity of nasal-sinus disease. As a result of the increased frequency of respiratory infection associated with allergic rhinitis, these patients are at risk for damage to the olfactory epithelium.

Taste confusions following gymnemic acid rinse.

The effect of a gymnemic acid (GA) rinse, which simulated a sweet-taste deficit, was measured on human taste perception and identification. Taste ratings showed that GA reduced the intensities of sucrose and aspartame to 14% of pre-rinse levels; over the recovery interval of 30 min, these values increased linearly to 63% of the pre-rinse levels. Repeated presentations of a set of 10 stimuli (five primarily or partly sweet--sucrose, aspartame, and NaCl-sucrose, acid-sucrose and quinine-sucrose mixtures; and five nonsweet--NaCl, KCl, Na glutamate (MSG), quinine HCl and citric acid) for identification following water and GA rinses produced 'taste confusion matrices' (TCMs). Correct identification of the sweet-tasting stimuli was reduced by 23% in presentations closely following the GA rinse, an effect that dissipated with time. Most misidentifications involved sucrose and mixtures containing sucrose. In a second TCM experiment, GA was presented frequently within each session to maintain the sweet taste deficit, which revealed itself as specific confusions. Rinsing with GA impaired discriminability of sweet-nonsweet pairs of stimuli but enhanced discriminability of the aspartame-(NaCl-sucrose) pair. GA had no effect on discriminability of nonsweet stimulus pairs. The results suggest that specific error patterns in the TCM could be used to identify quality-specific taste disorders.

Gustatory function after third molar extraction.

OBJECTIVE: The purpose of this study was to determine the severity and time course of taste changes after extraction of all 4 third molars. STUDY DESIGN: Taste function in 17 patients was measured before third molar surgery and at 1 month and 6 months after surgery. Two tests were administered: a whole-mouth, above-threshold test in which subjects sipped, expectorated, and then rated the intensities and identified the taste qualities of various solutions, and a localized test in which subjects rated and identified solutions painted with cotton swabs on different oral sites. RESULTS: Intensity ratings for solutions in the whole-mouth test were reduced by approximately 14% for NaCl, citric acid, and quinine hydrochloride at 1 month after surgery and had not recovered by 6 months after surgery for citric acid (P<.02). The taste quality of NaCl was identified correctly less frequently after third molar extraction. Perceived taste intensity on discrete areas of the tongue was significantly reduced after surgery (P<.05). Patients with the most severely impacted molars gave the lowest taste intensity ratings to whole-mouth test solutions at 6 months after surgery (P<.02). In contrast, taste function in a group of subjects who received only local dental anesthesia was not affected. CONCLUSIONS: Gustatory deficits occur after third molar extraction, persist for as long as 6 months after surgery, and appear to be associated with depth of impaction.

Topical corticosteroid treatment of anosmia associated with nasal and sinus disease.

OBJECTIVE: To establish the efficacy of topical corticosteroid nasal spray treatment of severe olfactory loss associated with severe nasal and sinus disease. DESIGN: Efficacy before and after open-label trial of topical corticosteroid nasal spray used exclusively in the head-down-forward position. SETTING: Taste and smell clinic of a university teaching hospital and research facility. PATIENTS: Taste and smell clinic patients with anosmia or severe hyposmia associated with paranasal sinus disease and nasal polyposis including 39 of 45 patients recruited from 1988 to 1994 who completed the topical corticosteroid treatment course and returned for subsequent testing. INTERVENTION: At least 8 weeks of treatment with flunisolide (Nasalide), 2 sprays in each nostril twice a day, with concurrent antibiotic treatment of any bacterial infection. MAIN OUTCOME MEASURES: Subjective olfactory symptoms, objective olfactory function tests, and otolaryngological evaluation (including endoscopic examination). RESULTS: Olfactory scores significantly improved following treatment (P < .001); signs of nasal and sinus disease significantly decreased (P < .001); and 26 (66%) of the patients reported a subjective improvement in their sense of smell. CONCLUSION: Topical corticosteroid nasal spray administered in a head-down-forward position is an effective treatment of severe olfactory loss associated with severe nasal and sinus disease.

Asthma among Puerto Rican Hispanics: a multi-ethnic comparison study of risk factors.

For a study of childhood asthma we interviewed 9,276 mothers during 1993-1994, ascertaining whether they had asthmatic children younger than 18 yr of age and asking about genetic and environmental risk factors for asthma. Independent risk factors for asthma in 7,776 children were: Hispanic and African American ethnicity, maternal history of asthma, lower socioeconomic status (SES) of the mother, and the presence of a cigarette smoker in the household. Hispanic ethnicity was also a strong risk factor for asthma in the mother. The prevalence of asthma among children of Hispanic (mainly Puerto Rican) mothers with one or more children older than 9 mo of age was 18.4%, for blacks it was 1 1.3%, and for non-Hispanic whites it was 7.4%. The marked increased risk for asthma in children of Hispanic mothers was not explained by SES or maternal age. In addition, increased risk for asthma in these children was not associated with higher reporting of environmental tobacco smoke (ETS) exposure. In this study of asthma in primarily Puerto Rican Hispanics, the risk of physician-diagnosed asthma as reported by mothers was significantly associated with Hispanic ethnicity, and it was not confounded by SES or active smoking in the home.

Olfactory sensitivity: reliability, generality, and association with aging.

Thirty-two Ss between 22 and 59 years of age yielded detection thresholds for 4 odorants over 4 sessions. The thresholds decreased and reliability increased over the course of testing. High intercorrelations between odorants and the stability of an S's relative position within the threshold distributions showed that a general factor of sensitivity dominated the outcome. Age contributed strongly to intersubject variation. Even among these nonelderly individuals, it accounted for up to 2 orders of magnitude in threshold performance. Other important factors included superiority of the right nostril and a negative correlation between the mean and variance of threshold distributions. Scant attention to the correlation may have contributed to overestimation of the frequency and specificity of specific anosmia. A clinically relevant outcome was that measurement of threshold for diagnostic purposes can generally rely on just 1 odorant.

Evaluation of olfactory dysfunction in the Connecticut Chemosensory Clinical Research Center.

The olfactory test administered to patients at the Connecticut Chemosensory Clinical Research Center combines stability of outcome with sensitivity to variables known to affect olfaction (age, sex). The test, which pairs an odor threshold component with an odor identification component, readily resolves differences in function between patients and controls. It reveals differences in the distribution of functioning for various probable causes (nasal/sinus disease, postupper respiratory infection, and head trauma), proves sensitive to improvements in function caused by therapeutic intervention (ethmoidectomy, steroid administration for nasal/sinus disease), and correlates with objective signs of nasal/sinus disease (visual exam, x-ray). The two components of the test agree well, though the odor identification component seems somewhat more sensitive than the threshold component as currently designed.

Taste and smell problems: validation of questions for the clinical history.

Complaints of taste and smell dysfunction unaccompanied by symptoms of neurological or nasal problems are not uncommon. However, "I can't taste" is not necessarily an accurate symptom description. Complaints tend to reflect the common confusion between taste sensations (that is, salt, sour, sweet, bitter) and flavor sensations (including taste, smell, temperature, and texture). A number of questions have been identified that help classify symptoms according to the type of dysfunction (taste, smell, or both): whether the problem is quantitative (reduced or absent sensation) or qualitative (distorted sensations); and what might have caused the dysfunction. Directed questioning can yield a clinical history that predicts chemosensory function and identifies the most likely cause of the problem. Questions were assessed by comparing the self-reports of taste and smell symptoms to the clinical evaluation of chemosensory function for 101 new patients seen in the Taste and Smell Center at the University of Connecticut Health Center in 1983.

Chemosensory dysfunction. Clinical evaluation results from a taste and smell clinic.

Findings from 441 patient evaluations performed at the Taste and Smell Clinic of the Connecticut Chemosensory Clinical Research Center are presented. Taste and smell dysfunction was the chief complaint in all patients. The diagnostic approach included tests of taste and smell function; history taking; physical, neurologic, otorhinolaryngologic, and nutritional examinations; and clinical laboratory screening tests. Results indicate that the most common chemosensory dysfunction is probably olfactory: 86% of patients in this series had measurable loss of smell function. The most common cause of olfactory deficit was nasal and/or sinus disease (30% of patients), followed by idiopathic conditions (26%) and prior upper respiratory infection (19%). Assessment of individual components of the evaluation suggests that a total circulating eosinophil count may be useful as a screening test for nasal and/or sinus disease among patients whose chief complaint is chemosensory dysfunction.