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Background: Antibiotic use remains common for the treatment of lower respiratory tract infections. The objective of this study was to evaluate the impact of antibiotic use on the duration and severity of acute lower respiratory tract infection (LRTI)., Participants: Adult patients presenting to US primary or urgent care sites with a chief complaint of cough and symptoms consistent with LRTI., Main Measures: Collected data included demographics, comorbidities, symptoms, and 48 viral and bacterial respiratory pathogens by PCR. Severity of signs/symptoms was reported for up to 28 days using diaries and text messages. Interpolation was used where data were missing., Key Results: Of 718 patients with baseline data, 29% had an antibiotic prescribed at baseline. The most common antibiotics were amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin in 85% of patients. Provision of an antibiotic had no effect on the duration or overall severity of cough, including in patients with viral, bacterial, and mixed infections. Receipt of an antibiotic did reduce the likelihood of a follow-up visit (14.1% vs 8.2%, aOR 0.47, 95% CI 0.26-0.84), perhaps by removing the motivation of getting an antibiotic at a follow-up visit. However, they were also more likely to receive a systemic corticosteroid (31.9% vs 4.5%, p < 0.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, p < 0.001). Patients believed that receiving an antibiotic would reduce the duration of their illness by nearly 4 days., Conclusions: In this large prospective study in the US primary and urgent care setting, antibiotics had no measurable impact on the severity or duration of cough due to acute LRTI. Patients had unrealistic expectations regarding the duration of LRTI and the effect of antibiotics which should be the target of antibiotic stewardship efforts., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Testing for influenza in patients with acute lower respiratory tract infection (LRTI) is common and in some cases is performed for all patients with LRTI. A more selective approach to testing could be more efficient., Methods: We used data from two prospective studies in the US primary and urgent care settings that enrolled patients with acute LRTI or influenza-like illness. Data were collected in the 2016, 2019, 2021, and 2022 flu seasons. All patients underwent polymerase chain reaction (PCR) testing for influenza and the FluScore was calculated based on patient-reported symptoms at their initial visit. The probability of influenza in each risk group was reported, as well as stratum-specific likelihood ratios (SSLRs) for each risk level., Results: The prevalence of influenza within risk groups varied based on overall differences in flu seasons and populations. However, the FluScore exhibited consistent performance across various seasons and populations based on the SSLRs. The FluScore had a consistent SSLR range of 0.20 to 0.23 for the low-risk group, 0.63 to 0.99 for the moderate-risk group, and 1.46 to 1.67 for the high-risk group. The diagnostic odds ratio based on the midpoints of these ranges was 7.25., Conclusions: The FluScore could streamline patient categorization, identifying patients who could be exempted from testing, while identifying candidates for rapid influenza tests. This has the potential to be more efficient than a "one size fits all" test strategy, as it strategically targets the use of tests on patients most likely to benefit. It is potentially usable in a telehealth setting., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Resistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence., Aim: To undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs., Methods: A systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs., Trial Registration: PROSPERO Registration number: CRD42023376769., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Boateng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Acute respiratory infections (ARIs) are the most common illness seen in the pediatric ambulatory setting. Research in this area is hampered by the lack of validated ARI measures. The aim of this study was to assess the reliability and validity of the Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K), a 15-item instrument, which measures illness-specific symptoms and impact on quality of life during an ARI., Methods: WURSS-K was administered to two populations: (1) children aged 4-10 years recruited from the local community and (2) 9- and 10-year-old children from an ongoing study, the Urban Environment and Childhood Asthma., Results: Overall, 163 children with 249 ARI episodes completed WURSS-K. WURSS-K was analyzed using multiple models to evaluate reliability and validity for a two-factor structure (symptom and functionality) and a single global structure. These models provided evidence of reliability and validity with omega of 0.72 and 0.91 for symptoms and functionality along with the single structure with omega of 0.90., Conclusions: WURSS-K shows strong psychometric properties for validity and reliability as either a single global factor or a two-factor structure. This instrument will be useful in both therapeutic trials and observational studies among children with ARI in ambulatory settings., Impact: WURSS-K is a valid and reliable illness-specific quality of life instrument that evaluates the impacts of ARIs on children. WURSS-K is designed for children 4-10 years of age, for whom there is a lack of validated assessment tools. This now validated instrument will be useful for future observational studies and therapeutic trials among children with ARIs in ambulatory settings., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Practice of meditation or exercise may enhance health to protect against acute infectious illness., Objective: To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness., Design: Randomized controlled prevention trial with three parallel groups., Setting: Madison, Wisconsin, USA., Participants: Community-recruited adults who did not regularly exercise or meditate., Methods: 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed., Results: Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control., Conclusions: Training in mindfulness meditation or exercise may help protect against ARI illness., Limitations: This trial was likely underpowered., Trial Registration: Clinicaltrials.gov NCT01654289., Competing Interests: The authors have declared that no competing interests exist.

Background: The inflammatory chemokine, interferon-gamma inducible protein of 10kDa (IP-10), is a biomarker associated with several conditions., Objectives: This study investigated serum concentrations of IP-10 in healthy individuals who developed acute respiratory infection (ARI). The hypothesis is that serum IP-10 concentrations correlate with ARI severity and detection of viral pathogens., Study Design: Data come from a randomized controlled trial measuring the effects of mindfulness meditation or exercise on ARI (Clinical Trials ID: NCT01654289). Healthy adults ages 30-69 were followed for a single season for ARI incidence and severity. This trial is ongoing, and the investigators are still blinded. When a participant reported ARI symptoms, nasal swab and lavage for PCR-based viral identification and blood samples were collected within the first 72h of ARI symptoms. Serum IP-10 concentrations were measured by ELISA (R&D Systems, Inc., Quantikine ELISA, Minneapolis, MN). ARI severity was measured using the validated Wisconsin Upper Respiratory Symptom Survey (WURSS-24) until the ARI episode resolved., Results: Serum IP-10 concentrations from 225 ARI episodes correlated with ARI global severity (rho 0.28 [95% CI: 0.15-0.39]; p<0.001). IP-10 concentrations were higher with an ARI in which a viral pathogen was detected compared to no viral pathogen detected (median 366pg/ml [IQR: 227-486] vs 163pg/ml [IQR: 127-295], p<0.0001). Influenza infections had higher IP-10 concentrations than coronavirus, enterovirus or rhinovirus, and paramyxovirus., Conclusion: Serum IP-10 concentration correlates with ARI global severity. Also, IP-10 concentration measured early in the course of the ARI correlates with the daily severity, duration, and illness symptoms., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: To assess the concurrent and predictive validity of the Nasal Mucus Index (NMI), a novel measurement of acute respiratory infection (ARI) severity., Objective: ARI, including the common cold and influenza, imposes a great burden on individuals and society. Previous research has attempted to assess the severity of ARI with self-reported and laboratory-based measurements. Self-reported measurements may introduce bias. Laboratory-based metrics are often expensive. Therefore, there is a need for non-self-reported, affordable, and validated ARI severity tests., Methods: Participants (N = 719) with an ARI episode underwent nasal lavage on days 1 and 3. The samples were visually assessed for the amount of mucus present in the sample and were given a subsequent NMI score. Collected samples were further assessed for interleukin (IL) 8 values (in pg/mL) and polymorphonuclear neutrophils (PMN) per high-power field. The participants rated episode severity and nasal symptoms daily by using the validated Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21). A subset of nasal symptoms was used as an additional comparator. NMI scores were compared with same-day IL-8 level, PMN count, and WURSS-21 scores for concurrent validation purposes by using the Spearman ρ as the index of correlation. NMI scores were correlated with overall episode severity measurements to assess predictive validity. Overall episode severity was measured as the WURSS-21 area under the curve, nasal symptoms area under the curve, and episode duration., Results: The NMI score correlated significantly with the same-day IL-8 level (ρ = 0.443, p < 0.001), PMN count (ρ = 0.498, p < 0.001), WURSS-21 score (ρ = 0.098, p = 0.004), and nasal symptom score (ρ = 0.162, p < 0.001). No significant predictive correlations were found., Conclusion: Associations with inflammatory biomarkers and self-reported severity measurements provided evidence of concurrent validity for the novel NMI score. The NMI can be used in future research as a simple, inexpensive, non-self-reported indicator of ARI severity.

Procalcitonin (PCT) is a biomarker of inflammation that is used to help make clinical decisions, like starting antibiotics or admitting a patient to the hospital. While PCT levels have been widely studied in pneumonia, levels in less severe acute respiratory infections (ARI) have not been well studied. To measure PCT levels in otherwise healthy adults during ARI, we followed 99 healthy adults during the cold and flu season, collecting blood specimens for PCT testing at baseline, and when participants presented with ARI. Ninety-six percent of the ARI samples had PCT levels <0.05 ng/mL. The remaining 4% were <0.25 ng/mL. These data suggest that PCT is not a useful test in ARI of mild-to-moderate severity.

Background: Poor mental health conditions, including stress and depression, have been recognized as a risk factor for the development of acute respiratory infection. Very few studies have considered the role of general mental health in acute respiratory infection occurrence. The aim of this analysis is to determine if overall mental health, as assessed by the mental component of the Short Form 12 Health Survey, predicts incidence, duration, or severity of acute respiratory infection., Methods: Data utilized for this analysis came from the National Institute of Health-funded Meditation or Exercise for Preventing Acute Respiratory Infection (MEPARI) and MEPARI-2 randomized controlled trials examining the effects of meditation or exercise on acute respiratory infection among adults aged > 30 years in Madison, Wisconsin. A Kendall tau rank correlation compared the Short Form 12 mental component, completed by participants at baseline, with acute respiratory infection incidence, duration, and area-under-the-curve (global) severity, as assessed by the Wisconsin Upper Respiratory Symptom Survey., Results: Participants were recruited from Madison, Wis, using advertisements in local media. Short Form 12 mental health scores significantly predicted incidence (P = 0.037) of acute respiratory infection, but not duration (P = 0.077) or severity (P = 0.073). The Positive and Negative Affect Schedule (PANAS) negative emotion measure significantly predicted global severity (P = 0.036), but not incidence (P = 0.081) or duration (P = 0.125). Mindful Attention Awareness Scale scores significantly predicted incidence of acute respiratory infection (P = 0.040), but not duration (P = 0.053) or severity (P = 0.70). The PHQ-9, PSS-10, and PANAS positive measures did not show significant predictive associations with any of the acute respiratory infection outcomes., Conclusion: Self-reported overall mental health, as measured by the mental component of Short Form 12, predicts acute respiratory infection incidence.

Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (r(s) = 0.082, P = 0.022; r(s)  = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = < 0.00001; r = 0.18, P = < 0.003), plugged nose (r = 0.045, P = 0.003; r = 0.14, P = 0.058), and sneezing (r = -0.02, P = < 0.0001; r = -0.0055, P = 0.31). Neutrophils correlate with some quality of life measures such as sleeping well (r = 0.15, P = 0.026). Thus, the study demonstrates that IL-8 and neutrophils are correlated with severity of nasal symptoms during acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness., (© 2014 Wiley Periodicals, Inc.)

Purpose: To develop a shorter version of the Wisconsin Upper Respiratory Symptom Survey (WURSS-21), a self-report questionnaire for evaluating daily symptoms and functional impairments during acute respiratory illness (ARI)., Methods: WURSS-21 data were retrieved from 4 studies (n = 1167) spanning the years 2002-2010. Similar methodologies were employed among these studies. Degree of missingness, ceiling/floor effects, and exploratory (EFA) and confirmatory (CFA) factor analyses were investigated and used to guide item retention. Stability of the reduced WURSS was evaluated across the first 3 days of ARI., Results: Degree of missingness was <1 % and appeared to be completely at random. Seven WURSS items with >30 % of ratings of zero (floor effects) were eliminated. Cross-loading items (head congestion, sleep well and breathe easily) were excluded following EFA on subset-1. Subsequent CFA using subset-2 showed satisfactory indices of fit. The reduced WURSS-11 instrument demonstrated 3 dimensions of 3 items each and was stable across 3 days of illness. The indicated dimensions (items) include nasal (runny nose, plugged nose, sneezing), throat (cough, sore throat, scratchy throat), and quality of life (feeling tired, think clearly, accomplish daily activities)., Conclusion: The WURSS-11 has similar dimensional structure as the WURSS-21. This shorter version may reduce the time and burden required for completing the survey.

Objectives: The role of bacteria in acute respiratory illnesses (ARI) of adults and interactions with viral infections is incompletely understood. This study tested the hypothesis that bacterial co-infection during ARI adds to airway inflammation and illness severity., Methods: Two groups of 97 specimens each were randomly selected from multiplex-PCR identified virus-positive and virus-negative nasal specimens obtained from adults with new onset ARI, and 40 control specimens were collected from healthy adults. All specimens were analyzed for Haemophilus influenzae(HI), Moraxella catarrhalis(MC) and Streptococcus pneumoniae(SP) by quantitative-PCR. General linear models tested for relationships between respiratory pathogens, biomarkers (nasal wash neutrophils and CXCL8), and ARI-severity., Results: Nasal specimens from adults with ARIs were more likely to contain bacteria (37% overall; HI = 28%, MC = 14%, SP = 7%) compared to specimens from healthy adults (5% overall; HI = 0%, MC = 2.5%, SP = 2.5%; p < 0.001). Among ARI specimens, bacteria were more likely to be detected among virus-negative specimens compared to virus-positive specimens (46% vs. 27%; p = 0.0046). The presence of bacteria was significantly associated with increased CXCL8 and neutrophils, but not increased symptoms., Conclusion: Pathogenic bacteria were more often detected in virus-negative ARI, and also associated with increased inflammatory biomarkers. These findings suggest the possibility that bacteria may augment virus-induced ARI and contribute to airway inflammation., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Acute respiratory infection (ARI) is among the most common, debilitating and expensive human illnesses. The purpose of this study was to assess ARI-related costs and determine if mindfulness meditation or exercise can add value., Methods: One hundred and fifty-four adults ≥50 years from Madison, WI for the 2009-10 cold/flu season were randomized to (i) wait-list control (ii) meditation or (iii) moderate intensity exercise. ARI-related costs were assessed through self-reported medication use, number of missed work days and medical visits. Costs per subject were based on cost of generic medications, missed work days ($126.20) and clinic visits ($78.70). Monte Carlo bootstrap methods evaluated reduced costs of ARI episodes., Results: The total cost per subject for the control group was $214 (95% CI: $105-$358), exercise $136 (95% CI: $64-$232) and meditation $65 (95% CI: $34-$104). The majority of cost savings was through a reduction in missed days of work. Exercise had the highest medication costs at $16.60 compared with $5.90 for meditation (P = 0.004) and $7.20 for control (P = 0.046). Combining these cost benefits with the improved outcomes in incidence, duration and severity seen with the Meditation or Exercise for Preventing Acute Respiratory Infection study, meditation and exercise add value for ARI. Compared with control, meditation had the greatest cost benefit. This savings is offset by the cost of the intervention ($450/subject) that would negate the short-term but perhaps not long-term savings., Conclusions: Meditation and exercise add value to ARI-associated health-related costs with improved outcomes. Further research is needed to confirm results and inform policies on adding value to medical spending.

Purpose: This study was designed to evaluate potential preventive effects of meditation or exercise on incidence, duration, and severity of acute respiratory infection (ARI) illness., Methods: Community-recruited adults aged 50 years and older were randomized to 1 of 3 study groups: 8-week training in mindfulness meditation, matched 8-week training in moderate-intensity sustained exercise, or observational control. The primary outcome was area-under-the-curve global illness severity during a single cold and influenza season, using the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) to assess severity. Health care visits and days of missed work were counted. Nasal wash collected during ARI illness was assayed for neutrophils, interleukin-8, and viral nucleic acid., Results: Of 154 adults randomized into the study, 149 completed the trial (82% female, 94% white, mean age 59.3 ± 6.6 years). There were 27 ARI episodes and 257 days of ARI illness in the meditation group (n = 51), 26 episodes and 241 illness days in the exercise group (n = 47), and 40 episodes and 453 days in the control group (n = 51). Mean global severity was 144 for meditation, 248 for exercise, and 358 for control. Compared with control, global severity was significantly lower for meditation (P = .004). Both global severity and total days of illness (duration) trended toward being lower for the exercise group (P=.16 and P=.032, respectively), as did illness duration for the meditation group (P=.034). Adjusting for covariates using zero-inflated multivariate regression models gave similar results. There were 67 ARI-related days of-work missed in the control group, 32 in the exercise group (P = .041), and 16 in the meditation group (P <.001). Health care visits did not differ significantly. Viruses were identified in 54% of samples from meditation, 42% from exercise, and 54% from control groups. Neutrophil count and interleukin-8 levels were similar among intervention groups., Conclusions: Training in meditation or exercise may be effective in reducing ARI illness burden.

OBJECTIVES. To review the evidence regarding the effectiveness of orally ingested Echinacea extracts in reducing the incidence, severity, or duration of acute upper respiratory infections (URIs). SEARCH STRATEGIES. Information from a wide range of sources was used as background material. More than 100 articles, books, and book chapters were reviewed for content and further references. Database searches, bibliographic reviews, and conversations with experts were carried out iteratively from January 1997 to February 1999. SELECTION CRITERIA. Published or unpublished reports of all blinded placebo-controlled randomized trials of any Echinacea formulation used as a treatment or for the prevention of URIs. DATA COLLECTION AND ANALYSIS. Review considerations included randomization, blinding, power, validity and clinical relevance of outcome measurements, inclusion and exclusion criteria, indistinguishability of treatment and placebo, and appropriateness of conclusions for the data presented. MAIN RESULTS. Nine treatment trials and 4 prevention trials fitting the selection criteria were found. Eight of the treatment trials reported generally positive results, and 3 of the prevention trials reported marginal benefit. Methodologic quality of the majority of the trials was modest. CONCLUSIONS. Evidence from published trials suggests that Echinacea may be beneficial for the early treatment of acute URIs. The influence of publication bias on those results is unknown. Echinacea preparations vary widely in composition, and are often found in combination with other potentially active constituents, making specific dose recommendations problematic. There is very little evidence supporting the prolonged use of Echinacea for the prevention of URIs. [ABSTRACT FROM AUTHOR]