Clinical and laboratory factors associated with coronavirus disease 2019 (Covid-19): A systematic review and meta-analysis.

SARS Coronavirus-2 is one of the most widespread viruses globally during the 21st century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.

SARS-CoV-2 RNAaemia in children: An Iranian referral hospital-based study.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS-CoV-2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS-CoV-2 RNA detection in blood in 96 pediatric patients with confirmed COVID-19. Among all patients, 6 (6%) had SARS-CoV-2 RNAaemia. Out of the six patients with SARS-CoV-2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS-CoV-2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID-19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS-CoV-2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS-CoV-2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS-CoV-2 RNAemia with area under the curve  levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS-CoV-2 RNAaemia showed a severe COVID-19 and one-third of the patients with SARS-CoV-2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS-CoV-2 RNAaemia.

Neurological features and outcome in COVID-19: dementia can predict severe disease.

The COVID-19 pandemic has infected more than 22 million people worldwide. Although much has been learned about COVID-19, we do not know much about its neurological features and their outcome. This observational study was conducted on the patients of Imam Hossein Hospital, and 361 adult patients (214 males) with confirmed diagnosis of COVID-19 from March 5, 2020 to April 3, 2020, were enrolled. Data was gathered on age, sex, comorbidities, initial symptoms, symptoms during the disease course, neurological symptoms, and outcome. The mean age of the patients was 61.90 ± 16.76 years. The most common initial symptoms were cough, fever, and dyspnea. In 21 patients (5.8%), the initial symptom was neurological. History of dementia was associated with severe COVID-19 disease (odds ratio = 1.28). During the course of the disease, 186 patients (51.52%) had at least one neurological symptom, the most common being headache (109 [30.2%]), followed by anosmia/ageusia (69, [19.1%]), and dizziness (54, [15%]). Also, 31 patients had neurological complications (8.58%). Anosmia, ageusia, dizziness, and headache were associated with favorable outcome (P < 0.001), while altered mental status and hemiparesis were associated with poor outcome. The mortality rate of patients who had neurological complications was more than twice than that of patients without neurological complication (P = 0.008). Almost half of the patients experienced at least one neurological symptom, which may be the initial presentation of COVID-19. Dementia appears to be associated with severe COVID-19. Mortality was higher in patients with neurological complications, and these patients needed more intensive care.

Prognostic value of serum amyloid A in patients with COVID-19.

OBJECTIVE: To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). METHODS: The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. RESULTS: The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z1 = - 1.426, P = 0.154. The Z1 values (Z1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were - 5.569, - 6.967, and - 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. CONCLUSION: SAA can be used as a predictor of the prognosis in patients with COVID-19.

Clinical characteristics of 194 cases of COVID-19 in Huanggang and Taian, China.

PURPOSE: We aimed to report the clinical characteristics of 194 cases coronavirus disease-19 (COVID-19) in Huanggang, Hubei and Taian, Shandong. METHODS: We retrospectively investigated the clinical, laboratory characteristics and CT imaging of confirmed cases of COVID-19 from January 22 to February 28, 2020 in Huanggang Central Hospital and The Second Affiliated Hospital of Shandong First Medical University. Real time PCR was used to detect the new coronavirus in respiratory samples. Immunohistochemical staining was used to detect the expressions of ACE2 in tissues. RESULTS: Among the 194 patients infected with COVID-19, 108 patients were male, with a median age of 48.3 years. The average preclinical period was 7.44 day. Except for 37 severe or critically ill patients, the rest of the 157 patients exhibited mild or moderate symptoms. 190 (97.94%) patients were confirmed during the three times nucleic acid test. The main clinical symptom of the patients were fever, sore throat and cough, which accounted for 146 cases (75.26%), 98 (50.52%) and 86 cases (44.33%), respectively. 30 patients (15.46%) showed liver dysfunction. Imaging examination showed that 141 patients (72.68%) showed abnormal density shadow, while 53 cases (27.32%) had no obvious abnormality in the parenchyma of both lungs. Up to now, 109 cases have been discharged from the hospital, and 9 patients died. The ACE2 expression levels were up-regulated in patients of severe type and critically ill type. CONCLUSION: Clinical symptoms, laboratory tests and CT imaging should be combined for comprehensive analysis to diagnose COVID-19. ACE2 may be the receptor of COVID-19.

Clinical and demographic characteristics of patients with COVID-19 infection: Statistics from a single hospital in Iran.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in early 2020. This infectious disorder has a heterogeneous course ranging from asymptomatic disorder to a critical situation needing intensive cares. In the current study, we present a report of affected patients admitted in a single hospital in Iran. Eighty-two hospitalized patients with COVID-19 were assessed. Demographic, clinical, and paraclinical parameters were gathered and statistically analyzed. The median age (IQR) of the patients was 57.32 (45.75, 70) years. At primary evaluation, fever was present in 45.12% of the affected individuals. The most common clinical symptoms were dyspnea (81.71%) and cough (65.85%). Totally, 12 (14.63%) and 14 (17.07%) of patients had low and high WBC counts, respectively. Lymphopenia was detected in 36 (43.9%) of patients, while 6 (7.32%) of patients had lymphocytosis. High levels of Il-6 were detected in 4 (4.88%) of patients. CRP levels were elevated in 69 (84.1%) of patients. The median (IQR) of hospitalization was 7 (5, 9) days. Totally, 26 patients (31%) were hospitalized in ICU. All patients were discharged with good health conditions except for one patient who died. The current study shows the heterogeneous clinical manifestations and paraclinical parameters of COVID-19 patients.

Respiratory symptoms and mortality in four general population cohorts over 45 years.

OBJECTIVE: This study assessed the association between respiratory symptoms and mortality in four cohorts of the general population in Norway aged 15-75 years and in selected subgroups in the pooled sample. METHODS: The study comprised 158,702 persons, who were drawn randomly from the Norwegian population register. All subjects received a standardized, self-administered questionnaire on 11 respiratory symptoms between 1972 and 1998, with follow-up of death until December 31, 2017. Analyses were performed on 114,380 respondents. RESULTS: The hazard of death was closely associated with sex, age, and education. The hazard ratios (HR) for death and the 95% confidence intervals (CI) by risk factors were similar in the four cohorts. After adjustment for demographic and environmental, modifiable factors, the HR for death was 1.90 (95% CI 1.80-2.00) for breathlessness score 3, 1.28 (1.21-1.37) for cough/phlegm score 5 and 1.09 (1.05-1.14) for attack of breathlessness/wheeze score 2 compared to the referent (no symptom), respectively. The cough/phlegm score was associated with death in current smokers but not in never smokers or ex-smokers. Breathlessness score was associated with death in men and women. CONCLUSION: Among persons aged 45-75 years, respiratory symptoms were significant predictors of all cause mortality. Education and smoking habits influenced only the associations between coughing and mortality. The associations were independent of study sites.

Chronic bronchitis before age 50 years predicts incident airflow limitation and mortality risk.

BACKGROUND: Previous studies on the relationship of chronic bronchitis to incident airflow limitation and all-cause mortality have provided conflicting results, with positive findings reported mainly by studies that included populations of young adults. This study sought to determine whether having chronic cough and sputum production in the absence of airflow limitation is associated with onset of airflow limitation, all-cause mortality and serum levels of C-reactive protein (CRP) and interleukin-8 (IL-8), and whether subjects' age influences these relationships. METHODS: 1412 participants in the long-term Tucson Epidemiological Study of Airway Obstructive Disease who at enrolment (1972-1973) were 21-80 years old and had FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) > or = 70% and no asthma were identified. Chronic bronchitis was defined as cough and phlegm production on most days for > or = 3 months in two or more consecutive years. Incidence of airflow limitation was defined as the first follow-up survey with FEV(1)/FVC <70%. Serum IL-8 and CRP levels were measured in cryopreserved samples from the enrolment survey. RESULTS: After adjusting for covariates, chronic bronchitis at enrolment significantly increased the risk for incident airflow limitation and all-cause mortality among subjects <50 years old (HR 2.2, 95% CI 1.3 to 3.8; and HR 2.2, 95% CI 1.3 to 3.8; respectively), but not among subjects > or = 50 years old (HR 0.9, 95% CI 0.6 to 1.4; and HR 1.0, 95% CI 0.7 to 1.3). Chronic bronchitis was associated with increased IL-8 and CRP serum levels only among subjects <50 years old. CONCLUSIONS: Among adults <50 years old, chronic bronchitis unaccompanied by airflow limitation may represent an early marker of susceptibility to the effects of cigarette smoking on systemic inflammation and long-term risk for chronic obstructive pulmonary disease and all-cause mortality.

Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients.

OBJECTIVE: This study aimed to analyze the clinical characteristics and prognosis of pediatric idiopathic pulmonary hemosiderosis (IPH). METHODS: Pediatric IPH cases that were diagnosed at West China Second University Hospital, Sichuan University between 1996 and 2017 were reviewed. Follow-up data from 34 patients were collected. RESULTS: A total of 107 patients were included (42 boys and 65 girls). The median age was 6 years at diagnosis. The main manifestations of the patients were as follows: anemia (n = 100, 93.45%), cough (n = 68, 63.55%), hemoptysis (n = 61, 57%), fever (n = 23, 21.5%), and dyspnea (n = 23, 21.5%). There were relatively few pulmonary signs. The positive rates of hemosiderin-laden macrophages in sputum, gastric lavage fluid, and bronchoalveolar lavage fluid were 91.66%, 98.21%, and 100%, respectively. Seventy-nine patients were misdiagnosed. A total of 105 patients were initially treated with glucocorticoids, among whom 102 survived and three died. Among the followed up patients, two died and 32 survived, among whom 10 presented with recurrent episodes. CONCLUSIONS: The classic triad of pediatric IPH is not always present. The rates of misdiagnosis and recurrence of IPH are high. Early recognition and adequate immunosuppressive therapy are imperative for improving prognosis of IPH.

Seasons and ALS time of death.

INTRODUCTION: Respiratory complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Season-associated-death risk was not addressed before. OBJECTIVE: To assess month/season-associated death risk in ALS. METHODS: We included all patients followed in our unit who died before 1 January 2016, excluding those with uncertain information. A χ2 test assessed differences between months/seasons. A two-step cluster analysis explored the significant survival independent factors. Values of p < 0.05 or p < 0.01 (multiple comparisons) were considered significant. RESULTS: From 778 patients, 543 had died at censor date. Absolute death number was 46,46,37,47,38,50,41,43,41,48,40,66, for each month from January to December. No significant difference existed when considering all months and seasons globally (p > 0.05). Significant differences were found comparing December (highest rate, 12.2%) with March, May, July, August, September, November (p < 0.05). Deaths were higher in winter than in spring (p = 0.031), but similar between winter and summer (p = 0.16), and winter and autumn (p = 0.087). Bulbar-onset patients had a relatively increased death rate in summer, while spinal-onset patients died more frequently in winter. DISCUSSION: Death risk factors are probably dehydration for patients with dysphagia during summer and respiratory infections for patients with weak cough during winter. Flu vaccination, better ventilatory/cough assistance in winter and hydration in summer are recommended.

Excess mortality and tuberculosis among individuals with prolonged cough: a population-based study from Vietnam.

SETTING: A demographic surveillance site in north-west Vietnam. OBJECTIVES: To compare notification rates of sputum smear-positive tuberculosis (TB) and mortality rates between the general population and individuals with prolonged cough. DESIGN: A cohort study of 559 prolonged cough cases in a total population of 35,832, observed over 2.5 years. Outcome measures were sputum smear-positive TB and death. RESULTS: The age-standardised smear-positive TB notification rate among cough cases (553/100,000 person-years [py], 95%CI 268-1143) was significantly higher than in the general population (50/100,000 py, 95%CI 43-57), with a relative risk of 11.06 (95%CI 8.28-14.77). Among those who had a chest X-ray suggestive of TB but negative sputum smears prior to the study start, the rate was 6542/100,000 py (95%CI 2906-12,511). The cough cohort had a 2.61 (95%CI 2.38-2.87) times higher risk of dying than the general population. CONCLUSIONS: Individuals with prolonged cough in this study run a significantly increased risk of developing infectious TB and of dying. We recommend further evaluations of improved follow-up systems aimed at identifying and treating sputum smear-negative TB cases before they convert to an infectious stage.

High mortality and prevalence of HIV and tuberculosis in adults with chronic cough in Malawi: a cohort study.

BACKGROUND: Adults with suspected tuberculosis (TB) in health facilities in Africa have a high risk of death. The risk of death for adults with suspected TB at community-level is not known but may also be high. METHODS: Adults reporting cough of ⩾ 2 weeks (coughers) during a household census of 19,936 adults in a poor urban setting in Malawi were randomly sampled and age-frequency matched with adults without cough ⩾ 2 weeks (controls). At 12 months, participants were traced to establish vital status, offered human immunodeficiency virus (HIV) testing and investigated for TB if symptomatic (sputum for Xpert(®) MTB/RIF, smear microscopy and culture). RESULTS: Of 345 individuals with cough, 245 (71%) were traced, as were 243/345 (70.4%) controls. TB was diagnosed in 8.9% (16/178) of the coughers and 3.7% (7/187) of the controls (P = 0.039). HIV prevalence among coughers was 34.6% (56/162) and 18.8% (32/170) in controls (P = 0.005); of those who were HIV-positive, respectively 26.8% and 18.8% were newly diagnosed. The 12-month risk of death was 4.1% (10/245) in coughers and 2.5% (6/243) in controls (P = 0.317). CONCLUSION: Undiagnosed HIV and TB are common among adults with chronic cough, and mortality is high in this urban setting. Interventions that promote timely seeking of HIV and TB care are needed.

Smoking-related interstitial lung disease.

BACKGROUND: Smoking-related interstitial lung diseases (SR-ILDs) are a heterogeneous group of diseases with major clinical significance. Reliable epidemiological data are not yet available. METHOD: Review of pertinent literature retrieved by a selective search in PubMed. RESULTS: The available data on many aspects of SR-ILDs are sparse, but recent studies on the pathophysiology and targeted treatment of these conditions have revealed ways in which clinical outcomes can be improved. Highresolution computerized tomography should be used for differential diagnosis; lung biopsy is often unnecessary. Oncogenic mutations play a role in the pathogenesis of pulmonary Langerhans-cell histiocytosis (PLCH). In the future, cladribine and vemurafenib may be treatment options for PLCH. Desquamative interstitial pneumonia (DIP) may be difficult to distinguish from respiratorybronchiolitis-associated interstitial lung disease (RB-ILD); DIP is treated with steroids and sometimes with immune suppressants. In idiopathic pulmonary fibrosis (IPF), the antifibrotic drugs pirfenidone and nintedanib can delay disease progression. Smoking is also a risk factor for combined pulmonary fibrosis and emphysema (CPFE), rheumatoid-arthritis-associated interstitial lung disease (RA-ILD), pulmonary alveolar proteinosis (PAP), acute eosinophilic pneumonia (AEP), and diffuse alveolar hemorrhage (DAH) in Goodpasture syndrome. CONCLUSION: In smokers with exertional dyspnea and/or a nonproductive cough, SR-ILDs must be considered in the differential diagnosis. If an SR-ILD is suspected, the patient should be referred to a pulmonary specialist. Early treatment and smoking cessation can improve clinical outcomes, particularly in the acute and chronically progressive types of SR-ILD.

Subjects with COPD and productive cough have an increased risk for exacerbations and death.

BACKGROUND: Chronic bronchitis is related to worse general health status, exacerbations and mortality among subjects with COPD. Also less longstanding cough and phlegm may be related to worse prognosis in COPD but this has rarely been evaluated in population-based studies. AIM: To evaluate the relationship between productive cough, exacerbations and mortality among subjects with and without COPD. METHOD: All subjects with COPD (n = 993) were identified together with sex- and age matched reference subjects without obstructive lung function impairment from four population-based cohorts in 2002-04. Baseline spirometry and structured interview including data on exacerbations last 12 months were used in this study (n = 1986) together with mortality data collected until February 2012. RESULTS: Productive cough was more common in COPD than non-COPD (42.8 vs. 23.5%, p < 0.001), more common in men than women, but associated to exacerbations in both sexes. COPD-subjects with productive cough had the highest risk for exacerbations in both sexes and they had a significantly increased risk for death (HR 1.48, 95% CI 1.13-1.94) also when adjusted for sex, age, BMI, smoking habits and heart disease. CONCLUSION: Productive cough was common and increased the risk for exacerbations in both sexes, in both COPD and non-COPD. COPD-subjects with productive cough had the highest risk for exacerbations and a significantly higher risk for death also after adjustment for common risk factors.

Dietary vitamin A intake and the risk of mortality among children.

Increased consumption of dietary vitamin A is advocated as a long-term solution to vitamin A deficiency. We prospectively examined the relationship of dietary vitamin A intake and child mortality among 28,753 Sudanese children aged 6 mo to 6 y, who participated in a trial of vitamin A supplementation. After 18 mo of follow-up, 232 children died. Total dietary vitamin A intake was strongly and inversely associated with risk of mortality. The age- and sex-adjusted relative risk (RR) of mortality for a comparison of children in extreme quintiles was 0.35 (95% CIs 0.21-0.60; P for trend over quintiles < 0.0001). Even after possible confounding by socioeconomic variables was adjusted for, vitamin A intake was significantly protective (multi-variate relative risk 0.53). Dietary vitamin A intake was especially protective among children who were wasted and stunted or who had diarrhea or cough. These prospective data support an important role of dietary vitamin A in reducing childhood mortality in developing countries.

Randomized controlled trial of the effect of daily supplementation with zinc or multiple micronutrients on the morbidity, growth, and micronutrient status of young Peruvian children.

BACKGROUND: Zinc supplements reduce childhood morbidity in populations in whom zinc deficiency is common. In such populations, deficiencies in other micronutrients may also occur. OBJECTIVE: The objective was to determine whether the administration of other micronutrients with zinc modifies the effect of zinc supplementation on children's morbidity and physical growth. DESIGN: Two hundred forty-six children aged 6-35 mo with persistent diarrhea were randomly assigned to 1 of 3 groups to receive a daily supplement of 10 mg Zn alone (Zn; n = 81), zinc plus vitamins and other minerals at 1-2 times recommended daily intakes (Zn+VM; n = 82), or placebo (n = 83) for approximately 6 mo after the diarrhea episode ended. Morbidity information was collected on weekdays. Weight, length, and other anthropometric indicators were measured monthly, and plasma zinc and other indicators of micronutrient status were measured at baseline and 6 mo. RESULTS: Supplement consumption was high ( approximately 90%) in all groups, although slightly more vomiting was reported in the Zn+VM group (P < 0.0001, analysis of variance). The change in plasma zinc from baseline to 6 mo was greater in the 2 zinc groups (6.1, 27.3, and 16.2 micro g/dL in the placebo, Zn, and Zn+VM groups, respectively; P < 0.0001, analysis of variance). The Zn group had fewer episodes of diarrhea, dysentery, and respiratory illness and a lower prevalence of fever and cough than did the Zn+VM group and a lower prevalence of cough than did the placebo group (P = 0.05). No significant effects of supplementation on growth were observed. CONCLUSION: Morbidity was greater after supplementation with zinc plus multivitamins and minerals than it was after supplementation with zinc alone.

Morbidity and mortality in pups from pet stores and private sources: 968 cases (1987-1988).

Morbidity (greater than or equal to 1 disease condition) for pups sold from 3 pet stores from January 1987 through December 1988 ranged from 54 to 68%. In 1 store, morbidity was higher for store pups, compared with pups originating from private parties, for such disease conditions as "kennel cough," diarrhea, and several species of gastrointestinal parasites. In-store mortality ranged from 5 to 9.5% of pups arriving for sale.

Safety and efficacy of over-the-counter cough and cold medicines for use in children.

IMPORTANCE OF THE FIELD: Over-the-counter (OTC) cough and cold medications have been used widely for years and continue to be a preferred choice for temporary relief of symptoms of upper respiratory tract infections in children. These medications are being placed under extraordinary scrutiny in the pediatric population due to the lack of conclusive evidence about their therapeutic efficacy and increased reports of associations with serious adverse events and even mortality. AREAS COVERED IN THIS REVIEW: A PubMed search was conducted to identify articles published up to August 2009 describing the efficacy and safety of OTC cough and cold medications in children. The objective was to provide an overview of the relevant literature and regulatory history and to comment on the available data on this important topic. WHAT THE READER WILL GAIN: The paper provides a detailed up-to-date review of the key efficacy and safety studies published on the subject. In addition, the reader is presented with an overview of the regulatory history and recent developments surrounding the use of OTC cough and cold medications in children in the US. TAKE HOME MESSAGE: This review confirms the lack of efficacy of OTC cough and cold products in children and reaffirms that although the overall incidence of related serious adverse events is low, such events continue to occur. The conclusions in this paper support a recommendation that OTC cough and cold medications should not be given to infants and very young children. Furthermore, additional research is needed to evaluate the safety and efficacy of these medicines in the broader pediatric population.

Respiratory symptoms as predictors of all-cause mortality in an urban community: a 30-year follow-up.

OBJECTIVE: We investigated the relationship between respiratory symptoms and mortality from all causes in a large Norwegian population. We also examined mortality during separate periods of follow-up. DESIGN: Population-based, prospective cohort study. SETTING AND SUBJECTS: A total of 19,998 men and women were randomly selected from the general population of Oslo. They received a postal respiratory questionnaire. The response rate was 88%. MAIN OUTCOME MEASURES: The relationship between 11 respiratory symptoms and 30 years of total mortality was investigated separately for men and women by multivariate analyses with adjustment for age, smoking habits and occupational exposure to air pollution. RESULTS: The relative mortality risk in comparison with asymptomatic subjects varied from 1.36 (95% confidence interval 1.25-1.48) for cough symptoms to 2.46 (2.13-2.85) for severe dyspnoea amongst men; the corresponding rates amongst women were 1.28 (1.16-1.40) and 1.52 (1.31-1.75), respectively. The relative risk of mortality in individuals with 1-3, 4-6 and 7 or more symptoms was 1.20, 1.60 and 2.53 (P for trend 0.000) in men and 1.14, 1.47 and 1.84 (P for trend 0.000) in women. Except for cough, the mortality rates associated with respiratory symptoms decreased significantly during follow-up. The positive association between respiratory symptoms and mortality was observed in people with and without cardiopulmonary diseases. CONCLUSIONS: Respiratory symptoms were significant predictors of mortality from all causes over 30 years, decreased during follow-up and were still increased after 30 years.