Publications by authors named "Jordi Almirall"

43 Publications

Aspiration pneumonia: A renewed perspective and practical approach.

Respir Med 2021 Aug-Sep;185:106485. Epub 2021 May 26.

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Universitat de Barcelona, Barcelona, Spain; Service of Pneumology, Institut Clínic Del Torax, Institut D'Investigació Biomédica Agustí Pi I Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain. Electronic address:

Aspiration pneumonia (AP) is a sub-type of community-acquired pneumonia (CAP) still poorly recognized especially in the absence of an aspiration event. A further difficulty is the differentiation between AP and aspiration pneumonitis. From a clinical perspective, AP is becoming increasingly relevant as a potential cause of severe and life-threatening respiratory infection among frail and very old patients, particularly among those with CAP requiring inpatient care. Moreover, AP is frequently underdiagnosed and a clear-cut definition of this pathological entity is lacking. There are different factors that increase the risk for aspiration, but other common factors influencing oral colonization such as malnutrition, smoking, poor oral hygiene or dry mouth, are also important in the pathogenesis of AP and should be considered. While there is no doubt in the diagnosis of AP in cases of a recent witnessed aspiration of oropharyngeal or gastric content, we here proposed a definition of AP that also includes silent unobserved aspirations. For this reason, the presence of one or more risk factors of oropharyngeal aspiration is required together with one or more risk factors for oral bacterial colonization. This proposed definition based on expert opinion not only unifies the diagnostic criteria of AP, but also provides the possibility to devise easily applicable strategies to prevent oral colonization.
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January 2022

Validation of a Prediction Score for Drug-Resistant Microorganisms in Community-acquired Pneumonia.

Ann Am Thorac Soc 2021 02;18(2):257-265

Centro de Investigacíon Biomédica en Red de Enfermedades Respiratorias (CB06/06/0028), Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain.

Recommended initial empiric antimicrobial treatment covers the most common bacterial pathogens; however, community-acquired pneumonia (CAP) may be caused by microorganisms not targeted by this treatment. Developed in 2015, the PES (, extended-spectrum β-lactamase-producing , and methicillin-resistant ) score was developed in 2015 to predict the microbiological etiology of CAP caused by PES microorganisms. To validate the usefulness of the PES score for predicting PES microorganisms in two cohorts of patients with CAP from Valencia and Mataró. We analyzed two prospective observational cohorts of patients with CAP from Valencia and Mataró. Patients in the Mataró cohort were all admitted to an intensive care unit (ICU). Of the 1,024 patients in the Valencia cohort, 505 (51%) had a microbiological etiology and 31 (6%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.81 (95% confidence interval [95% CI], 0.74-0.88). For a PES score ≥5, sensitivity, specificity, the negative and positive predictive values as well as the negative and positive likelihood ratios were 72%, 74%, 98%, 14%, 0.38, and 2.75, respectively. Of the 299 patients in the Mataró cohort, 213 (71%) had a microbiological etiology and 11 (5%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.73 (95% CI 0.61-0.86). For a PES score ≥ 5, sensitivity, specificity, the negative and positive predictive values, and the negative and positive likelihood ratios were 36%, 83%, 96%, 11%, 0.77, and 2.09, respectively. The best cutoff for patients admitted to the ICU was 4 points, which improved sensitivity to 86%. The hypothetical application of the PES score showed high rates of overtreatment in both cohorts (26% and 35%, respectively) and similar rates of undertreatment. The PES score showed good accuracy in predicting the risk for microorganisms that required different empirical therapy; however, its use as a single strategy for detecting noncore pathogens could lead to high rates of overtreatment. Given its high negative predictive value, the PES score may be used as a first step of a wider strategy that includes subsequent advanced diagnostic tests.
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February 2021

Early and Late Cardiovascular Events in Patients Hospitalized for Community-Acquired Pneumonia.

Arch Bronconeumol (Engl Ed) 2020 Sep 30;56(9):551-558. Epub 2019 Nov 30.

Servicio de Neumología, Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, España.

Introduction: Community-acquired pneumonia increases the risk of cardiovascular events (CVE). The objective of this study was to analyze host, severity, and etiology factors associated with the appearance of early and late events and their impact on mortality.

Method: Prospective multicenter cohort study in patients hospitalized for pneumonia. CVE and mortality rates were collected at admission, 30-day follow-up (early events), and one-year follow-up (late events).

Results: In total, 202 of 1,967 (10.42%) patients presented early CVE and 122 (6.64%) late events; 16% of 1-year mortality was attributed to cardiovascular disease. The host risk factors related to cardiovascular complications were: age ≥65 years, smoking, and chronic heart disease. Alcohol abuse was a risk factor for early events, whereas obesity, hypertension, and chronic renal failure were related to late events. Severe sepsis and Pneumonia Severity Index (PSI) ≥3 were independent risk factors for early events, and only PSI ≥3 for late events. Streptococcus pneumoniae was the microorganism associated with most cardiovascular complications. Developing CVE was an independent factor related to early (OR 2.37) and late mortality (OR 4.05).

Conclusions: Age, smoking, chronic heart disease, initial severity, and S. pneumoniae infection are risk factors for early and late events, complications that have been related with an increase of the mortality risk during and after the pneumonia episode. Awareness of these factors can help us make active and early diagnoses of CVE in hospitalized CAP patients and design future interventional studies to reduce cardiovascular risk.
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September 2020

Community-Acquired Pneumonia Patients at Risk for Early and Long-term Cardiovascular Events Are Identified by Cardiac Biomarkers.

Chest 2019 12 2;156(6):1080-1091. Epub 2019 Aug 2.

Pneumology Department, Hospital Clínic/Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Center for Biomedical Research Network in Respiratory Diseases (CIBERES, CB06/06/0028), Madrid, Spain.

Background: Community-acquired pneumonia (CAP) increases the risk of cardiovascular complications during and following the episode. The goal of this study was to determine the usefulness of cardiovascular and inflammatory biomarkers for assessing the risk of early (within 30 days) or long-term (1-year follow-up) cardiovascular events.

Methods: A total of 730 hospitalized patients with CAP were prospectively followed up during 1 year. Cardiovascular (proadrenomedullin [proADM], pro-B-type natriuretic peptide (proBNP), proendothelin-1, and troponin T) and inflammatory (interleukin 6 [IL-6], C-reactive protein, and procalcitonin) biomarkers were measured on day 1, at day 4/5, and at day 30.

Results: Ninety-two patients developed an early event, and 67 developed a long-term event. Significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6 were recorded in patients who developed cardiovascular events. Despite a decrease at day 4/5, levels remained steady until day 30 in those who developed late events. Biomarkers (days 1 and 30) independently predicted cardiovascular events adjusted for age, previous cardiac disease, Pao/Fio < 250 mm Hg, and sepsis: ORs (95% CIs), proendothelin-1, 2.25 (1.34-3.79); proADM, 2.53 (1.53-4.20); proBNP, 2.67 (1.59-4.49); and troponin T, 2.70 (1.62-4.49) for early events. For late events, the ORs (95% CIs) were: proendothelin-1, 3.13 (1.41-7.80); proADM, 2.29 (1.01-5.19); and proBNP, 2.34 (1.01-5.56). Addition of IL-6 levels at day 30 to proendothelin-1 or proADM increased the ORs to 3.53 and 2.80, respectively.

Conclusions: Cardiac biomarkers are useful for identifying patients with CAP at high risk for early and long-term cardiovascular events. They may aid personalized treatment optimization and for designing future interventional studies to reduce cardiovascular risk.
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December 2019

Impact of Lymphocyte and Neutrophil Counts on Mortality Risk in Severe Community-Acquired Pneumonia with or without Septic Shock.

J Clin Med 2019 May 27;8(5). Epub 2019 May 27.

Laboratory of Biomedical Research in Sepsis (BioSepsis), Hospital Clínico Universitario de Valladolid, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.

Background: Community-acquired pneumonia (CAP) is a frequent cause of death worldwide. As recently described, CAP shows different biological endotypes. Improving characterization of these endotypes is needed to optimize individualized treatment of this disease. The potential value of the leukogram to assist prognosis in severe CAP has not been previously addressed.

Methods: A cohort of 710 patients with CAP admitted to the intensive care units (ICUs) at Hospital of Mataró and Parc Taulí Hospital of Sabadell was retrospectively analyzed. Patients were split in those with septic shock ( = 304) and those with no septic shock ( = 406). A single blood sample was drawn from all the patients at the time of admission to the emergency room. ICU mortality was the main outcome.

Results: Multivariate analysis demonstrated that lymphopenia <675 cells/mm or <501 cells/mm translated into 2.32- and 3.76-fold risk of mortality in patients with or without septic shock, respectively. In turn, neutrophil counts were associated with prognosis just in the group of patients with septic shock, where neutrophils <8850 cells/mm translated into 3.6-fold risk of mortality.

Conclusion: lymphopenia is a preserved risk factor for mortality across the different clinical presentations of severe CAP (sCAP), while failing to expand circulating neutrophils counts beyond the upper limit of normality represents an incremental immunological failure observed just in those patients with the most severe form of CAP, septic shock.
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May 2019

Social Determinants of Community-acquired Pneumonia: Differences by Age Groups.

Arch Bronconeumol (Engl Ed) 2019 Aug 28;55(8):447-449. Epub 2019 Feb 28.

Hospital de Mataró, Consorci Sanitari del Maresme, Mataró, Barcelona, Spain.

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August 2019

Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome.

J Intensive Care Med 2020 Jun 26;35(6):588-594. Epub 2018 Apr 26.

Multidisciplinary Intensive Care, St James's University Hospital, Dublin, Ireland.

Objective: To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS).

Materials And Methods: Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models.

Results: The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P = .796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone.

Conclusion: After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS.
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June 2020

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).

Intensive Care Med 2018 04 9;44(4):438-448. Epub 2018 Apr 9.

Department I of Internal Medicine, Intensive Care Unit and Hemostasis, University Hospital of Cologne, Cologne, Germany.

Purpose: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP).

Methods: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L).

Results: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58-78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline.

Conclusions: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation.

Trial Registration: NCT01420744.
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April 2018

Initial Inflammatory Profile in Community-acquired Pneumonia Depends on Time since Onset of Symptoms.

Am J Respir Crit Care Med 2018 08;198(3):370-378

3 Centro de Investigación Biomédica En Red-Enfermedades Respiratorias CB06/06/0028, Madrid, Spain.

Rationale: Assessment of the inflammatory response can help the decision-making process when diagnosing community-acquired pneumonia (CAP), but there is a lack of information about the influence of time since onset of symptoms.

Objectives: We studied the impact of the number of days since onset of symptoms on inflammatory cytokines and biomarker concentrations at CAP diagnosis in hospitalized patients.

Methods: We performed a secondary analysis in two prospective cohorts including 541 patients in the derivation cohort and 422 in the validation cohort. The time since onset of symptoms was self-reported, and patients were classified as early presenters (<3 d) and nonearly presenters. Biomarkers (C-reactive protein [CRP] and procalcitonin [PCT] in both cohorts) and cytokines in the derivation cohort (IL-1, - 6, -8, -10, and tumor necrosis factor-α) were measured within 24 hours of hospital admission.

Measurements And Main Results: In early presenters, CRP was significantly lower, whereas PCT, IL-6, and IL-8 were higher. Nonearly presenters showed significantly lower PCT, IL-6, and IL-8 levels. In the validation cohort, CRP and PCT exhibited identical patterns: CRP levels were 36.4% greater in patients with 3 or more days since onset of symptoms than in those with less than 3 days since symptom onset in the derivation cohort and 38.2% in the validation cohort. PCT levels were 40% lower in patients with 3 or more days since onset of symptoms in the derivation cohort and 56% in the validation cohort.

Conclusions: Time since symptom onset modifies the systemic inflammatory profile at CAP diagnosis. This information has relevant clinical implications for management, and it should be taken into account in the design of future clinical trials.
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August 2018

Oral health and risk of pneumonia in asthmatic pacients with inhaled treatment.

Med Clin (Barc) 2018 06 23;150(12):455-459. Epub 2017 Sep 23.

Unidad de Cuidados Intensivos, Hospital de Mataró, Consorcio Sanitario del Maresme, Mataró, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Barcelona, España.

Introduction And Objective: Asthma is a chronic disease requiring inhaled treatment and in addition it is a risk factor (RF) of pneumonia. In the oropharyngeal cavity there are numerous species of bacteria that could be dragged to the bronco-alveolar level.

Objective: to decide whether oral health is a community acquired pneumonia (CAP) RF in asthmatic patients who are taking inhaled treatment, and determining whether the frequency of use of inhalation devices and the type of inhaled drug are CAP RF.

Patients And Method: Case-control study in asthmatic population with inhaled treatment. We recruited 126 asthmatic patients diagnosed with pneumonia by clinical and radiological criteria (cases) and 252 asthmatics not diagnosed with pneumonia during the last year (controls), matched by age. The main factor of study was the General Oral Health Assessment Index (GOHAI) score.

Results: Bivariated analysis showed a statistically significant association of CAP with a GOHAI score≤57 points (poor oral health) (OR 1.69), anticholinergic treatment (OR 2.41), 6 or more inhalations (3.23), chamber use (OR 1.62), FEV (OR 0.98), altered functionality (OR 2.08) and psychiatric disorders or depression (OR 0.41). The multivariated analysis shows an independent association of performing 6 or more inhalations per day (OR 2.74) and functional impairment (OR 1.67).

Conclusions: The results suggest that poor oral health may be a CAP RF.
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June 2018

Risk Factors for Community-Acquired Pneumonia in Adults: A Systematic Review of Observational Studies.

Respiration 2017 25;94(3):299-311. Epub 2017 Jul 25.

Intensive Care Unit, Hospital de Mataró, Autonomous University of Barcelona, Consorci Sanitari del Maresme, Mataró, Spain.

We performed a systematic review of the literature to establish conclusive evidence of risk factors for community-acquired pneumonia (CAP). Observational studies (cross-sectional, case-control, and cohort studies) the primary outcome of which was to assess risk factors for CAP in both hospitalized and ambulatory adult patients with radiologically confirmed pneumonia were selected. The Newcastle-Ottawa Scale specific for cohort and case-control designs was used for quality assessment. Twenty-nine studies (20 case-control, 8 cohort, and 1 cross-sectional) were selected, with 44.8% of them focused on elderly subjects ≥65 years of age and 34.5% on mixed populations (participants' age >14 years). The median quality score was 7.44 (range 5-9). Age, smoking, environmental exposures, malnutrition, previous CAP, chronic bronchitis/chronic obstructive pulmonary disease, asthma, functional impairment, poor dental health, immunosuppressive therapy, oral steroids, and treatment with gastric acid-suppressive drugs were definitive risk factors for CAP. Some of these factors are modifiable. Regarding other factors (e.g., gender, overweight, alcohol use, recent respiratory tract infections, pneumococcal and influenza vaccination, inhalation therapy, swallowing disorders, renal and liver dysfunction, diabetes, and cancer) no definitive conclusion could be established. Prompt assessment and correction of modifiable risk factors could reduce morbidity and mortality among adult CAP patients, particularly among the elderly.
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July 2018

Gamma globulin fraction of the proteinogram and chronic obstructive pulmonary disease exacerbations.

Med Clin (Barc) 2017 Aug 21;149(3):107-113. Epub 2017 Feb 21.

Departamento de Medicina, Universidad Autónoma de Barcelona, Barcelona, España; Unidad de Cuidados Intensivos, Hospital de Mataró-Consorci Sanitari del Maresme, Mataró, Barcelona, España.

Objectives: To evaluate the levels of the serum gamma globulin fraction in proteinograms as a biomarker to assess the severity, and to predict the mortality and new exacerbations in patients admitted for an exacerbation of a COPD.

Patients And Methods: The VIRAE study was carried out on a cohort of patients hospitalized for an exacerbation of probable infectious origin of COPD over a period of 2 years. The levels of the serum gamma globulin fraction were analyzed in the proteinogram of 120 patients. The main clinical indicators of severity were also evaluated. Key features were compared in 2 groups (gamma fraction in the proteinogram greater or less than 6.6g/dl).

Results: The levels of the serum gamma fraction in the proteinogram correlated with the FEV (P=.009), the CRP (P=.04), and the number of readmissions after 6 months of hospitalization (P=.04). We observed a good association with the GOLD scale, the BODE index and the mMRC dyspnea scale; and also with treatment with oral corticoids and home oxygen therapy. We did not find it to be a good predictor of mortality, despite observing increased mortality rates one year after hospital admission in patients with low levels of the factor.

Conclusions: The levels of the gamma globulin fraction in proteinograms has a good correlation with the FEV. In addition, they are associated with a greater severity of patients with COPD. This simple biomarker may be useful in identifying high-risk patients.
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August 2017

Serum levels of immunoglobulins and severity of community-acquired pneumonia.

BMJ Open Respir Res 2016 28;3(1):e000152. Epub 2016 Nov 28.

Department of Biochemistry , Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró , Barcelona , Spain.

Instruction: There is evidence of a relationship between severity of infection and inflammatory response of the immune system. The objective is to assess serum levels of immunoglobulins and to establish its relationship with severity of community-acquired pneumonia (CAP) and clinical outcome.

Methods: This was an observational and cross-sectional study in which 3 groups of patients diagnosed with CAP were compared: patients treated in the outpatient setting (n=54), patients requiring in-patient care (hospital ward) (n=173), and patients requiring admission to the intensive care unit (ICU) (n=191).

Results: Serum total IgG (and IgG subclasses IgG1, IgG2, IgG3, IgG4), IgA and IgM were measured at the first clinical visit. Normal cutpoints were defined as the lowest value obtained in controls (≤680, ≤323, ≤154, ≤10, ≤5, ≤30 and ≤50 mg/dL for total IgG, IgG1, IgG2, IgG3, IgG4, IgM and IgA, respectively). Serum immunoglobulin levels decreased in relation to severity of CAP. Low serum levels of total IgG, IgG1 and IgG2 showed a relationship with ICU admission. Low serum level of total IgG was independently associated with ICU admission (OR=2.45, 95% CI 1.4 to 4.2, p=0.002), adjusted by the CURB-65 severity score and comorbidities (chronic respiratory and heart diseases). Low levels of total IgG, IgG1 and IgG2 were significantly associated with 30-day mortality.

Conclusions: Patients with severe CAP admitted to the ICU showed lower levels of immunoglobulins than non-ICU patients and this increased mortality.
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November 2016

IgG2 as an independent risk factor for mortality in patients with community-acquired pneumonia.

J Crit Care 2016 10 13;35:115-9. Epub 2016 May 13.

Unidad Medicina Intensiva, Hospital de Mataró, Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain; Ciber Enfermedades Respiratorias (CIBERES), Barcelona, Spain. Electronic address:

Background: Mortality in patients with community-acquired pneumonia (CAP) remains high despite improvements in treatment.

Objective: To determine immunoglobulin levels in patients with CAP and impact on disease severity and mortality.

Methodology: Observational study. Hospitalized patients with CAP were followed up for 30 days. Levels of immunoglobulin G (IgG) and subclasses, immunoglobulin A (IgA) and immunoglobulin M (IgM) were measured in serum within 24 hours of CAP diagnosis.

Results: Three hundred sixty-two patients with CAP were enrolled -172 ward-treated and 190 intensive care unit-treated. Intensive care unit-treated patients had significantly lower values of IgG1, IgG2, IgG3 subclasses, and IgA than ward-treated patients. Thirty-eight patients died before 30 days. Levels of IgG2 were significantly lower in non-survivors than survivors (P=.004) and IgG2 <301 mg/dL was associated with poorer survival according to both the bivariate (hazard ratio 4.47; P<.001) and multivariate (HR 3.48; P=.003) analyses.

Conclusions: Patients with CAP with IgG2 levels <301 mg/dL had a poorer prognosis and a higher risk of death. Our study suggests the usefulness of IgG2 to predict CAP evolution and to provide support measures or additional treatment.
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October 2016

[Epidemiology of community-acquired severe sepsis. A population-based study].

Med Clin (Barc) 2016 Aug 26;147(4):139-43. Epub 2016 May 26.

Servei de Medicina Intensiva, Hospital de Mataró, Mataró, Barcelona, España; Grup de Recerca en Sepsia, Imflamació i Seguretat, Escola Superior de Ciencies de la Salut, Mataró, Barcelona, España.

Background And Objective: Most studies aimed at getting to know the incidence of severe sepsis have methodological limitations which condition results that are difficult to compare and are inapplicable when it comes to estimating the necessary resources. Our objective is to evaluate the incidence and epidemiological aspects of community-acquired severe sepsis which require intensive care unit admission.

Patients And Method: Prospective observational population-based study in a population of 180,000 adults over 15 years old and a general hospital with 350 beds and 14 ICU beds. All episodes of community-acquired infection requiring admission to ICU due to severe sepsis were registered over a period of 9 years. The variables analyzed were: age, sex, SAPS II score, length of stay in ICU, type of infection, isolated microorganism, and deaths during their ICU admission. A statistical bivariate analysis and a multiple logistic regression were performed.

Results: Nine hundred and seventeen episodes with an average age of 65.2 years. The most frequent infectious focus was pulmonary (55.2%). The average SAPS II severity score index was 37.87 and mortality 19.7%. The annual incidence was 51.54 episodes per 100,000 adult inhabitants, meaning 1.97 ICU beds per day. In the multivariate analysis, the SAPS II score and a known aetiology were demonstrated as mortality risk factors.

Conclusions: This study brings us some epidemiological data from a population-based perspective which help us to care for patients better in our geographical area. The average annual incidence is 51.5 cases per 100,000 adult inhabitants which means that 2 ICU beds per day to attend this population.
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August 2016

Bacteraemia in outpatients with community-acquired pneumonia.

Eur Respir J 2016 Feb 5;47(2):654-7. Epub 2015 Nov 5.

Dept of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB) - SGR 911- Ciber de Enfermedades Respiratorias (Ciberes), Barcelona, Spain

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February 2016

Professions and Working Conditions Associated With Community-Acquired Pneumonia.

Arch Bronconeumol 2015 Dec 24;51(12):627-31. Epub 2014 Dec 24.

Institut Clínic del Tórax, Servei de Pneumologia, IDIBAPS, Hospital Clínic de Barcelona, CIBERES, Universitat de Barcelona, Barcelona, España. Electronic address:

Introduction: Community-acquired pneumonia (CAP) is not considered a professional disease, and the effect of different occupations and working conditions on susceptibility to CAP is unknown. The aim of this study is to determine whether different jobs and certain working conditions are risk factors for CAP.

Methodology: Over a 1-year period, all radiologically confirmed cases of CAP (n=1,336) and age- and sex-matched controls (n=1,326) were enrolled in a population-based case-control study. A questionnaire on CAP risk factors, including work-related questions, was administered to all participants during an in-person interview.

Results: The bivariate analysis showed that office work is a protective factor against CAP, while building work, contact with dust and sudden changes of temperature in the workplace were risk factors for CAP. The occupational factor disappeared when the multivariate analysis was adjusted for working conditions. Contact with dust (previous month) and sudden changes of temperature (previous 3 months) were risk factors for CAP, irrespective of the number of years spent working in these conditions, suggesting reversibility.

Conclusion: Some recent working conditions such as exposure to dust and sudden changes of temperature in the workplace are risk factors for CAP. Both factors are reversible and preventable.
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December 2015

Pneumonia as comorbidity in chronic obstructive pulmonary disease (COPD). Differences between acute exacerbation of COPD and pneumonia in patients with COPD.

Arch Bronconeumol 2014 Dec 25;50(12):514-20. Epub 2014 Oct 25.

Unidad de Cuidados Intensivos, Hospital de Mataró, Consorci Sanitari del Maresme, CIBERES, Mataró, Barcelona, España.

Introduction: Pneumonia is considered an independent entity in chronic obstructive pulmonary disease (COPD), to be distinguished from an infectious exacerbation of COPD. The aim of this study was to analyze the clinical characteristics and progress of the exacerbation of COPD (ECOPD) compared to pneumonia in COPD (PCOPD) patients requiring hospitalization.

Patients And Methods: Prospective, longitudinal, observational cohort study including 124 COPD patients requiring hospital admission for lower respiratory tract infection. Patients were categorized according to presence of ECOPD (n=104) or PCOPD (n=20), depending on presence of consolidation on X-ray. Demographic, clinical, laboratory, microbiological and progress variables were collected.

Results: Patients with ECOPD showed more severe respiratory disease according to the degree of obstruction (P<.01) and need for oxygen therapy (P<.05). PCOPD patients showed increased presence of fever (P<.05), lower blood pressure (P<.001), more laboratory abnormalities (P<.05; leukocytosis, elevated CRP, low serum albumin) and increased presence of crepitus (P<.01). Microbiological diagnosis was achieved in 30.8% of cases of ECOPD and 35% of PCOPD; sputum culture yielded the highest percentage of positive results, predominantly Pseudomonas aeruginosa. Regarding the progress of the episode, no differences were found in hospital stay, need for ICU or mechanical ventilation.

Conclusions: Our data confirm clinical and analytical differences between ECOPD and PCOPD in patients who require hospital admission, while there were no differences in subsequent progress.
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December 2014

Passive smoking at home is a risk factor for community-acquired pneumonia in older adults: a population-based case-control study.

BMJ Open 2014 Jun 13;4(6):e005133. Epub 2014 Jun 13.

Service of Pneumology, Institut Clínic del Torax, IDIBAPS, Hospital Clínic de Barcelona. Universitat de Barcelona, CIBERES, Barcelona, Spain.

Objective: To assess whether passive smoking exposure at home is a risk factor for community-acquired pneumonia (CAP) in adults.

Setting: A population-based case-control study was designed in a Mediterranean area with 860 000 inhabitants >14 years of age.

Participants: 1003 participants who had never smoked were recruited.

Primary And Secondary Outcome Measures: Risk factors for CAP, including home exposure to passive smoking, were registered. All new cases of CAP in a well-defined population were consecutively recruited during a 12-month period.

Methods: A population-based case-control study was designed to assess risk factors for CAP, including home exposure to passive smoking. All new cases of CAP in a well-defined population were consecutively recruited during a 12-month period. The subgroup of never smokers was selected for the present analysis.

Results: The study sample included 471 patients with CAP and 532 controls who had never smoked. The annual incidence of CAP was estimated to be 1.14 cases×10(-3) inhabitants in passive smokers and 0.90×10(-3) in non-passive smokers (risk ratio (RR) 1.26; 95% CI 1.02 to 1.55) in the whole sample. In participants ≥65 years of age, this incidence was 2.50×10(-3) in passive smokers and 1.69×10(-3) in non-passive smokers (RR 1.48, 95% CI 1.08 to 2.03). In this last age group, the percentage of passive smokers in cases and controls was 26% and 18.1%, respectively (p=0.039), with a crude OR of 1.59 (95% CI 1.02 to 2.38) and an adjusted (by age and sex) OR of 1.56 (95% CI 1.00 to 2.45).

Conclusions: Passive smoking at home is a risk factor for CAP in older adults (65 years or more).
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June 2014

Epidemiology, antibiotic therapy and clinical outcomes of healthcare-associated pneumonia in critically ill patients: a Spanish cohort study.

Intensive Care Med 2014 Apr 18;40(4):572-81. Epub 2014 Mar 18.

Area de Patología Crítica, Critical Care Department, Hospital de Sabadell, Corporació Sanitaria Universitaria Parc Taulí, Parc Taulí s/n, Sabadell, Spain,

Purpose: Information about healthcare-associated pneumonia (HCAP) in critically ill patients is scarce.

Methods: This prospective study compared clinical presentation, outcomes, microbial etiology, and treatment of HCAP, community-acquired pneumonia (CAP), and immunocompromised patients (ICP) with severe pneumonia admitted to 34 Spanish ICUs.

Results: A total of 726 patients with pneumonia (449 CAP, 133 HCAP, and 144 ICP) were recruited during 1 year from April 2011. HCAP patients had more comorbidities and worse clinical status (Barthel score). HCAP and ICP patients needed mechanical ventilation and tracheotomy more frequently than CAP patients. Streptococcus pneumoniae was the most frequent pathogen in all three groups (CAP, 34.2 %; HCAP, 19.5 %; ICP, 23.4 %; p = 0.001). The overall incidence of Gram-negative pathogens, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa was low, but higher in HCAP and ICP patients than CAP. Empirical treatment was in line with CAP guidelines in 73.5 % of patients with CAP, in 45.5 % of those with HCAP, and in 40 % of those with ICP. The incidence of inappropriate empirical antibiotic therapy was 6.5 % in CAP, 14.4 % in HCAP, and 21.8 % in ICP (p < 0.001). Mortality was highest in ICP (38.6 %) and did not differ between CAP (18.4 %) and HCAP (21.2 %).

Conclusions: HCAP accounts for one-fifth of cases of severe pneumonia in patients admitted to Spanish ICUs. The empirical antibiotic therapy recommended for CAP would be appropriate for 90 % of patients with HCAP in our population, and consequently the decision to include coverage of multidrug-resistant pathogens for HCAP should be cautiously judged in order to prevent the overuse of antimicrobials.
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April 2014

Community-acquired pneumonia among smokers.

Arch Bronconeumol 2014 Jun 31;50(6):250-4. Epub 2013 Dec 31.

Servicio de Neumología, Hospital Universitario Miguel Servet, CIBERES, Zaragoza, España.

Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection, even in passive smokers. This relationship also shows a dose-response effect, since the risk reduces spectacularly 10 years after giving up smoking, returning to the level of non-smokers. Streptococcus pneumoniae is the causative microorganism responsible for community-acquired pneumonia (CAP) most frequently associated with smoking, particularly in invasive pneumococcal disease and septic shock. It is not clear how it acts on the progress of pneumonia, but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse. In CAP caused by Legionella pneumophila, it has also been observed that smoking is the most important risk factor, with the risk rising 121% for each pack of cigarettes smoked a day. Tobacco use may also favor diseases that are also known risk factors for CAP, such as periodontal disease and upper respiratory viral infections. By way of prevention, while giving up smoking should always be proposed, the use of the pneumococcal vaccine is also recommended, regardless of the presence of other comorbidities.
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June 2014

Microbial aetiology of healthcare associated pneumonia in Spain: a prospective, multicentre, case-control study.

Thorax 2013 Nov;68(11):1007-14

Servicio de Pneumologia, Hospital Clínic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain.

Introduction: Healthcare-associated pneumonia (HCAP) is actually considered a subgroup of hospital-acquired pneumonia due to the reported high risk of multidrug-resistant pathogens in the USA. Therefore, current American Thoracic Society/Infectious Diseases Society of America guidelines suggest a nosocomial antibiotic treatment for HCAP. Unfortunately, the scientific evidence supporting this is contradictory.

Methods: We conducted a prospective multicentre case-control study in Spain, comparing clinical presentation, outcomes and microbial aetiology of HCAP and community-acquired pneumonia (CAP) patients matched by age (±10 years), gender and period of admission (±10 weeks).

Results: 476 patients (238 cases, 238 controls) were recruited for 2 years from June 2008. HCAP cases showed significantly more comorbidities (including dysphagia), higher frequency of previous antibiotic use in the preceding month, higher pneumonia severity score and worse clinical status (Charslon and Barthel scores). While microbial aetiology did not differ between the two groups (HCAP and CAP: Streptococcus pneumoniae: 51% vs 55%; viruses: 22% vs 12%; Legionella: 4% vs 9%; Gram-negative bacilli: 5% vs 4%; Pseudomonas aeruginosa: 4% vs 1%), HCAP patients showed worse mortality rates (1-month: HCAP, 12%; CAP 5%; 1-year: HCAP, 24%; CAP, 9%), length of hospital stay (9 vs 7 days), 1-month treatment failure (5.5% vs 1.5%) and readmission rate (18% vs 11%) (p<0.05, each).

Conclusions: Despite a similar clinical presentation, HCAP was more severe due to patients' conditions (comorbidities) and showed worse clinical outcomes. Microbial aetiology of HCAP did not differ from CAP indicating that it is not related to increased mortality and in Spain most HCAP patients do not need nosocomial antibiotic coverage.
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November 2013

Serum immunoglobulins in the infected and convalescent phases in community-acquired pneumonia.

Respir Med 2013 Dec 18;107(12):2038-45. Epub 2013 Sep 18.

Critical Care Service, Hospital de Mataró, Universitat Autònoma de Barcelona, CIBERES, Barcelona, Spain. Electronic address:

Background: A population-based case-control study was designed to assess changes of serum levels of immunoglobulins and IgG subclasses between infected and convalescent phase in community-acquired pneumonia (CAP).

Methods: Over a 2-year period, all subjects who were >14 years of age living in the Maresme region (Barcelona, Spain) diagnosed of CAP were registered. Controls were healthy subjects selected from the municipal census. Prognostic factors were assessed and serum levels of total IgG, IgA, IgM, and IgG subclasses were measured at diagnosis and 1 month later (cases).

Results: We studied 171 patients with CAP and 90 controls. All immunoglobulins were significantly lower in cases than in controls. At diagnosis, 42.7% of cases showed low levels of some immunologic parameter, mainly total IgG and IgG2. Low immunoglobulin levels at diagnosis were more frequent in patients requiring in-patient care and in those with pneumonia of other etiology than Streptococcus pneumoniae. In the convalescent phase, 26 (23.6%) patients normalized immunological levels. In 27 (24.5%) cases, some parameter with low levels persisted especially in patients with etiology of CAP other than S. pneumoniae.

Conclusions: Low serum levels of immunoglobulins particularly total IgG and IgG2 were a common finding in patients with CAP compared to healthy controls. Low immunoglobulin levels may be related to CAP prognosis and persisted in the convalescent phase in one-fourth of cases.
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December 2013

Relationship between the use of inhaled steroids for chronic respiratory diseases and early outcomes in community-acquired pneumonia.

PLoS One 2013 5;8(9):e73271. Epub 2013 Sep 5.

Critical Care Unit, Universitat Autònoma de Barcelona, CIBERES, Barcelona, Spain.

Background: The role of inhaled steroids in patients with chronic respiratory diseases is a matter of debate due to the potential effect on the development and prognosis of community-acquired pneumonia (CAP). We assessed whether treatment with inhaled steroids in patients with chronic bronchitis, COPD or asthma and CAP may affect early outcome of the acute pneumonic episode.

Methods: Over 1-year period, all population-based cases of CAP in patients with chronic bronchitis, COPD or asthma were registered. Use of inhaled steroids were registered and patients were followed up to 30 days after diagnosis to assess severity of CAP and clinical course (hospital admission, ICU admission and mortality).

Results: Of 473 patients who fulfilled the selection criteria, inhaled steroids were regularly used by 109 (23%). In the overall sample, inhaled steroids were associated with a higher risk of hospitalization (OR=1.96, p = 0.002) in the bivariate analysis, but this effect disappeared after adjusting by other severity-related factors (adjusted OR=1.08, p=0.787). This effect on hospitalization also disappeared when considering only patients with asthma (OR=1.38, p=0.542), with COPD alone (OR=4.68, p=0.194), but a protective effect was observed in CB patients (OR=0.15, p=0.027). Inhaled steroids showed no association with ICU admission, days to clinical recovery and mortality in the overall sample and in any disease subgroup.

Conclusions: Treatment with inhaled steroids is not a prognostic factor in COPD and asthmatic patients with CAP, but could prevent hospitalization for CAP in patients with clinical criteria of chronic bronchitis.
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June 2014

Oropharyngeal dysphagia is a risk factor for readmission for pneumonia in the very elderly persons: observational prospective study.

J Gerontol A Biol Sci Med Sci 2014 Mar 5;69(3):330-7. Epub 2013 Jul 5.

Research Unit, Consorci Sanitari del Maresme, Hospital de Mataró, Carretera de Cirera s/n, 08304, Mataró, Barcelona, Spain.

Background: To determine whether oropharyngeal dysphagia is a risk factor for readmission for pneumonia in elderly persons discharged from an acute geriatric unit.

Methods: Observational prospective cohort study with data collection based on clinical databases and electronic clinical notes. All elderly individuals discharged from an acute geriatric unit from June 2002 to December 2009 were recruited and followed until death or December 31, 2010. All individuals were initially classified according to the presence of oropharyngeal dysphagia assessed by bedside clinical examination. Main outcome measure was readmission for pneumonia. Clinical notes were reviewed by an expert clinician to verify diagnosis and classify pneumonia as aspiration or nonaspiration pneumonia.

Results: A total of 2,359 patients (61.9% women, mean age 84.9 y) were recruited and followed for a mean of 24 months. Dysphagia was diagnosed in 47.5% of cases. Overall, 7.9% of individuals were readmitted for pneumonia during follow-up, 24.2% of these had aspiration pneumonia. The incidence rate of hospital readmission for pneumonia was 3.67 readmissions per 100 person-years (95% CI 3.0-4.4) in individuals without dysphagia and 6.7 (5.5-7.8) in those with dysphagia, with an attributable risk of 3.02 readmissions per 100 person-years (1.66-4.38) and a rate ratio of 1.82 (1.41-2.36). Multivariate Cox regression showed an independent effect of oropharyngeal dysphagia, with a hazard ratio of 1.6 (1.15-2.2) for hospitalization for pneumonia, 4.48 (2.01-10.0) for aspiration pneumonia, and 1.44 (1.02-2.03) for nonaspiration pneumonia.

Conclusion: Oropharyngeal dysphagia is a very prevalent and relevant risk factor associated with hospital readmission for both aspiration and nonaspiration pneumonia in the very elderly persons.
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March 2014

The use of benzodiazepines could be a protective factor for community-acquired pneumonia (CAP) in ≤ 60-year-old subjects.

Thorax 2013 Oct 4;68(10):964-5. Epub 2013 May 4.

Intensive Care Unit, Hospital de Mataró, , Mataró, Barcelona, Spain, CIBERES Spain.

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October 2013

Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial.

Lancet Infect Dis 2013 Feb 19;13(2):123-9. Epub 2012 Dec 19.

Primary Care and Population Sciences Division, University of Southampton, Southampton, UK.

Background: Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older.

Methods: Patients older than 18 years with acute lower-respiratory-tract infections (cough of ≤28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated "moderately bad" or worse. Secondary outcomes were symptom severity in days 2-4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N).

Findings: 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated "moderately bad" or worse (hazard ratio 1.06, 95% CI 0.96-1.18; p=0.229) nor mean symptom severity (1.69 with placebo vs 1.62 with amoxicillin; difference -0.07 [95% CI -0.15 to 0.007]; p=0.074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15.9%] of 1021 patients vs 194 [19.3%] of 1006; p=0.043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11-174; p=0.025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595).

Interpretation: When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms.

Funding: European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.
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February 2013

Airway obstruction and bronchodilator responsiveness in adults with acute cough.

Ann Fam Med 2012 Nov-Dec;10(6):523-9

University Medical Center Utrecht, Julius Center for Health, Sciences and Primary Care, Utrecht, the Netherlands.

Purpose: We sought to determine the prevalence of airway obstruction and bronchodilator responsiveness in adults consulting for acute cough in primary care.

Methods: Family physicians recruited 3,105 adult patients with acute cough (28 days or shorter) attending primary care practices in 12 European countries. After exclusion of patients with preexisting physician-diagnosed asthma or chronic obstructive pulmonary disease (COPD), we undertook complete case analysis of spirometry results (n = 1,947) 28 to 35 days after inclusion. Bronchodilator responsiveness was diagnosed if there were recurrent complaints of wheezing, cough, or dyspnea and an increase of the forced expiratory volume in 1 second (FEV(1)) of 12% or more after bronchodilation. Airway obstruction was diagnosed according to 2 thresholds for the (postbronchodilator) ratio of FEV(1) to forced vital capacity (FEV(1):FVC): less than 0.7 and less than the lower limit of normal.

Results: There were 240 participants who showed bronchodilator responsiveness (12%), 193 (10%) had a FEV(1)/FVC ratio of less than 0.7, and 126 (6%) had a ratio of less than the lower limit of normal. Spearman's correlation between the 2 definitions of obstruction was 0.71 (P <.001), with discordance most pronounced among those younger than 30 years and in older participants.

Conclusions: Both bronchodilator responsiveness and persistent airway obstruction are common in adults without established asthma or COPD who consult for acute cough in primary care, which suggests a high risk of undiagnosed asthma and COPD. Different accepted methods to define airway obstruction detected different numbers of patients, especially at the extremes of age. As both conditions benefit from appropriate and timely interventions, clinicians should be aware and responsive to potential underdiagnosis.
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March 2013

Incidental chest radiographic findings in adult patients with acute cough.

Ann Fam Med 2012 Nov-Dec;10(6):510-5

University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands.

Purpose: Imaging may produce unexpected or incidental findings with consequences for patients and ordering of future investigations. Chest radiography in patients with acute cough is among the most common reasons for imaging in primary care, but data on associated incidental findings are lacking. We set out to describe the type and prevalence of incidental chest radiography findings in primary care patients with acute cough.

Methods: We report on data from a cross-sectional study in 16 European primary care networks on 3,105 patients with acute cough, all of whom were undergoing chest radiography as part of a research study workup. Apart from assessment for specified signs of pneumonia and acute bronchitis, local radiologists were asked to evaluate any additional finding on the radiographs. For the 2,823 participants with good-quality chest radiographs, these findings were categorized according to clinical relevance based on previous research evidence and analyzed for type and prevalence by network, sex, age, and smoking status.

Results: Incidental findings were reported in 19% of all participants, and ranged from 0% to 25% by primary care network, with the network being an independent contributor (P <.001). Of all participants 3% had clinically relevant incidental findings. Suspected nodules and shadows were reported in 1.8%. Incidental findings were more common is older participants and smokers (P <. 001).

Conclusions: Clinically relevant incidental findings on chest radiographs in primary care adult patients with acute cough are uncommon, and prevalence varies by setting.
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March 2013