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Introduction Long-term use of nebulized or oral antibiotics is common in the treatment of cystic fibrosis and non-cystic fibrosis bronchiectasis. To date, however, few studies have focused on the use of nebulized antibiotics in COPD patients. The aims of this study are: to establish whether a combination of nebulized colistin plus continuous cyclic azithromycin in severe COPD patients with chronic bronchial infection due to Pseudomonas aeruginosa reduces the frequency of exacerbations, and to assess the effect of this treatment on microbiological sputum isolates. Material and methods A retrospective cohort was created for the analysis of patients with severe COPD and chronic bronchial infection due to P. aeruginosa treated with nebulized colistin at the Respiratory Day Care Unit between 2005 and 2015. The number and characteristics of COPD exacerbations (ECOPD) before and up to two years after the introduction of nebulized colistin treatment were recorded. Results We analyzed 32 severe COPD patients who received nebulized colistin for at least three months (median 17 months [IQR 7-24]). All patients but one received combination therapy with continuous cyclic azithromycin (median 24 months [IQR 11-30]). A significant reduction in the number of ECOPD from baseline of 38.3% at two years of follow-up was observed, with a clear decrease in P. aeruginosa ECOPD (from 59.5% to 24.6%) and a P. aeruginosa eradication rate of 28% over the two-year follow-up. Conclusion In patients with severe COPD and chronic bronchial infection due to P. aeruginosa, combination therapy with nebulized colistin and continuous cyclic azithromycin significantly reduced the number of ECOPD, with a marked decrease in P. aeruginosa sputum isolates.

Objectives: To determine the prevalence, comorbidities, biomarkers characterization and costs of severe asthma in patients ≥12-year-old in real life. Methods: Retrospective, cross-sectional, nationwide study that used a top-down approach. Data from BIG-PAC® database (Real Life Data) were used, which is an electronic medical record of 1.9 million Spanish patients (pts) aged ≥12 who had demanded medical care during 2017. Severe asthma (SA) was defined as asthma that required GINA step 5 treatment. Uncontrolled pts were defined by GINA 2019 criteria and oral corticosteroid (OCS) dependent pts were defined by prescription of OCS for at least 6 months. Biomarkers such as blood eosinophils, Fractional Exhaled Nitric Oxide (FeNO) and Immunoglobulin E (IgE) were used to phenotype type 2 pts. Results: The prevalence of asthma was 5.5%. Of these, SA was 7.7%, of whom: 64.1% had uncontrolled SA; 81.2% presented type 2 asthma; 31.2% were OCS-dependent (37% in the uncontrolled SA group); The most common type 2 comorbidities were allergic rhinitis (66.1%), atopic dermatitis (29.1%) and CRSwNP (14.6%). Biologics were administered in 3.8% of total SA patients and 4.3% of patients of the uncontrolled group. The mortality rate was 4.2% and 5.5% in the total SA and the uncontrolled SA group respectively. The total annual costs per patient for uncontrolled SA were 6.010€ and 2.791€ in the controlled SA pts. Conclusions: A vast majority of SA pts present with type-2 asthma. SA continues to have high rates of uncontrolled and OCS dependent asthma despite new available treatments. Uncontrolled SA costs twice as much as controlled pts.

Background and objective Non-Invasive Ventilation (NIV) represents a standard of care to treat some acute respiratory failure (ARF). Data on its use in pneumonia are lacking, especially in a setting outside the Intensive Care Unit (ICU). The aims of this study were to evaluate the use of NIV in ARF due to pneumonia outside the ICU, and to identify risk factors for in-hospital mortality. Methods Prospective, observational study performed in 19 centers in Italy. Patients with ARF due to pneumonia treated outside the ICU with either continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NPPV) were enrolled over a period of at least 3 consecutive months in 2013. Independent factors related to in-hospital mortality were evaluated. Results Among the 347 patients enrolled, CPAP was applied as first treatment in 176 (50.7%) patients,NPPV in 171 (49.3%). The NPPV compared with CPAP group showed a significant higher PaCO2 (55 [47–78] vs 37 [32–43] mmHg, p Conclusions Outside ICU setting, CPAP was used mainly for hypoxemic non-hypercapnic ARF, NPPV for hypercapnic ARF. In-hospital mortality was mainly associated to patients' basal status (DNI status, CCI) rather than the baseline degree of ARF.

We compared the bacterial microbiomes lodged in the bronchial tree, oropharynx and nose of patients with early stage cystic fibrosis (CF) not using chronic antibiotics, determining their relationships with lung function and exacerbation frequency. CF patients were enrolled in a cohort study during stability and were checked regularly over the following 9 months. Upper respiratory samples (sputum [S], oropharyngeal swab [OP] and nasal washing [N]) were collected at the first visit and every 3 months. 16S rRNA gene amplification and sequencing was performed and analyzed with QIIME. Seventeen CF patients were enrolled (16.6 SD 9.6 years). Alpha-diversity of bacterial communities between samples was significantly higher in S than in OP (Shannon index median 4.6 [IQR: 4.1–4.9] vs. 3.7 [IQR: 3-1-4.1], p = 0.003/Chao 1 richness estimator median 97.75 [IQR: 85.1–110.9] vs. 43.9 [IQR: 31.7–59.9], p = 0.003) and beta-diversity analysis also showed significant differences in the microbial composition of both respiratory compartments (Adonis test of Bray Curtis dissimilarity matrix, p = 0.001). Dominant taxa were found at baseline in five patients (29.4%), who showed lower forced expiratory volume in the first second (FEV1%, mean 74.8 [SD 19] vs. 97.2 [SD 17.8], p = 0.035, Student t test). The Staphylococcus genus had low RAs in most samples (median 0.26% [IQR 0.01–0.69%]), but patients with RA > 0.26% of Staphylococcus in bronchial secretions suffered more exacerbations during follow-up (median 2 [IQR 1–2.25] vs. 0 [0–1], p = 0.026. Mann–Whitney U test), due to S. aureus in more than a half of the cases, microorganism that often persists as bronchial colonized in these patients (9/10 [90%] vs. 2/7 [28.6%], p = 0.034, Fisher’s exact test). In conclusion, the bronchial microbiome had significantly higher diversity than the microbial flora lodged in the oropharynx in early stage CF. Although the RA of the Staphylococcus genus was low in bronchial secretions and did not reach a dominance pattern, slight overrepresentations of this genus was associated with higher exacerbation frequencies in these patients.

Objective: To investigate the applicability of ultrasound imaging of the diaphragm in interstitial lung disease (ILD). Methods: Using ultrasound, we compared ILD patients and healthy volunteers (controls) in terms of diaphragmatic mobility during quiet and deep breathing; diaphragm thickness at functional residual capacity (FRC) and at total lung capacity (TLC); and the thickening fraction (TF, proportional diaphragm thickening from FRC to TLC). We also evaluated correlations between diaphragmatic dysfunction and lung function variables. Results: Between the ILD patients (n = 40) and the controls (n = 16), mean diaphragmatic mobility was comparable during quiet breathing, although it was significantly lower in the patients during deep breathing (4.5 ± 1.7 cm vs. 7.6 ± 1.4 cm; p < 0.01). The patients showed greater diaphragm thickness at FRC (p = 0.05), although, due to lower diaphragm thickness at TLC, they also showed a lower TF (p < 0.01). The FVC as a percentage of the predicted value (FVC%) correlated with diaphragmatic mobility (r = 0.73; p < 0.01), and an FVC% cut-off value of < 60% presented high sensitivity (92%) and specificity (81%) for indentifying decreased diaphragmatic mobility. Conclusions: Using ultrasound, we were able to show that diaphragmatic mobility and the TF were lower in ILD patients than in healthy controls, despite the greater diaphragm thickness at FRC in the former. Diaphragmatic mobility correlated with ILD functional severity, and an FVC% cut-off value of < 60% was found to be highly accurate for indentifying diaphragmatic dysfunction on ultrasound.

Objective: Early tuberculosis diagnosis and treatment are determinants of better outcomes and effective disease control. Although tuberculosis should ideally be managed in a primary care setting, a proportion of patients are diagnosed in emergency facilities (EFs). We sought to describe patient characteristics by place of tuberculosis diagnosis and determine whether the place of diagnosis is associated with treatment outcomes. A secondary objective was to determine whether municipal indicators are associated with the probability of tuberculosis diagnosis in EFs. Methods: We analyzed data from the São Paulo State Tuberculosis Control Program database for the period between January of 2010 and December of 2013. Newly diagnosed patients over 15 years of age with pulmonary, extrapulmonary, or disseminated tuberculosis were included in the study. Multiple logistic regression models adjusted for potential confounders were used in order to evaluate the association between place of diagnosis and treatment outcomes. Results: Of a total of 50,295 patients, 12,696 (25%) were found to have been diagnosed in EFs. In comparison with the patients who had been diagnosed in an outpatient setting, those who had been diagnosed in EFs were younger and more socially vulnerable. Patients diagnosed in EFs were more likely to have unsuccessful treatment outcomes (adjusted OR: 1.54; 95% CI: 1.42-1.66), including loss to follow-up and death. At the municipal level, the probability of tuberculosis diagnosis in EFs was associated with low primary care coverage, inequality, and social vulnerability. In some municipalities, more than 50% of the tuberculosis cases were diagnosed in EFs. Conclusions: In the state of São Paulo, one in every four tuberculosis patients is diagnosed in EFs, a diagnosis of tuberculosis in EFs being associated with poor treatment outcomes. At the municipal level, an EF diagnosis of tuberculosis is associated with structural and socioeconomic indicators, indicating areas for improvement.

To identify pathogens that require different treatments in community-acquired pneumonia (CAP), we propose an acronym, "PES" (Pseudomonas aeruginosa, Enterobacteriaceae extended-spectrum β-lactamase-positive, and methicillin-resistant Staphylococcus aureus).To compare the clinical characteristics and outcomes between patients with CAP caused by PES versus other pathogens, and to identify the risk factors associated with infection caused by PES.We conducted an observational prospective study evaluating only immunocompetent patients with CAP and an established etiological diagnosis. We included patients from nursing homes. We computed a score to identify patients at risk of PES pathogens.Of the 4,549 patients evaluated, we analyzed 1,597 who presented an etiological diagnosis. Pneumonia caused by PES was identified in 94 (6%) patients, with 108 PES pathogens isolated (n = 72 P. aeruginosa, n = 15 Enterobacteriaceae extended-spectrum β-lactamase positive, and n = 21 methicillin-resistant Staphylococcus aureus). These patients were older (P = 0.001), had received prior antibiotic treatment more frequently (P 0.001), and frequently presented with acute renal failure (P = 0.004). PES pathogens were independently associated with increased risk of 30-day mortality (adjusted odds ratio = 2.51; 95% confidence interval = 1.20-5.25; P = 0.015). The area under the curve for the score we computed was 0.759 (95% confidence interval, 0.713-0.806; P 0.001).PES pathogens are responsible for a small proportion of CAP, resulting in high mortality. These pathogens require a different antibiotic treatment, and identification of specific risk factors could help to identify these microbial etiologies.

Rationale: The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown. Objectives: To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia. Methods: This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality. Measurements and Main Results: Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the "treat-all" strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality. Conclusions: qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile.

ICUAP includes pneumonia acquired during ICU stays of patients under mechanical ventilation (ventilator-associated pneumonia, or VAP), as well as of non-ventilated patients (NV-ICUAP). Although the current literature contains few studies examining NV-ICUAP, it has been suggested that both diagnoses present with similar pathogens and, depending on case-mix, similar outcomes.

Thoracentesis is one of the bedside procedures most commonly associated with iatrogenic complications, particularly pneumothorax. Various risk factors for complications associated with thoracentesis have recently been identified, including an inexperienced operator; an inadequate or inexperienced support team; the lack of a standardized protocol; and the lack of ultrasound guidance. We sought to determine whether ultrasound-guided thoracentesis can reduce the risk of pneumothorax and improve outcomes (fewer procedures without fluid removal and greater volumes of fluid removed during the procedures). In our comparison of thoracentesis with and without ultrasound guidance, all procedures were performed by a team of expert pulmonologists, using the same standardized protocol in both conditions.A total of 160 participants were randomly allocated to undergo thoracentesis with or without ultrasound guidance (n = 80 per group). The primary outcome was pneumothorax following thoracentesis. Secondary outcomes included the number of procedures without fluid removal and the volume of fluid drained during the procedure.Pneumothorax occurred in 1 of the 80 patients who underwent ultrasound-guided thoracentesis and in 10 of the 80 patients who underwent thoracentesis without ultrasound guidance, the difference being statistically significant (p = 0.009). Fluid was removed in 79 of the 80 procedures performed with ultrasound guidance and in 72 of the 80 procedures performed without it. The mean volume of fluid drained was larger during the former than during the latter (960 ± 500 mL vs. 770 ± 480 mL), the difference being statistically significant (p = 0.03).Ultrasound guidance increases the yield of thoracentesis and reduces the risk of post-procedure pneumothorax. (Chinese Clinical Trial Registry identifier: ChiCTR-TRC-12002174 [http://www.chictr.org/en/]).

Background and objective Although the benefits of systemic corticosteroids in community-acquired pneumonia (CAP) are not clear, their use is frequent in clinical practice. We described the frequency of this practice, patients' characteristics and its clinical impact. Methods We investigated all adult CAP patients visited between June 1997 and January 2008 (n = 3257). Results Two hundred and sixty patients received systemic corticosteroids (8%) with a mean daily dose of 45 (33) mg (median, 36 mg/day). Patients receiving corticosteroids were older (74 (13) vs 65 (19) years), had more comorbidities (respiratory, 59% vs 38%, cardiac, 29% vs 16%, etc.), higher Pneumonia Severity Index (Fine IV–V, 76% vs 50%) and had received inhaled corticosteroids (36% vs 15%) and previous antibiotics (31% vs 23%) more frequently (P

Despite improvements in the management of community-acquired pneumonia (CAP), morbidity and mortality are still high, especially in patients with more severe disease. Early and appropriate antibiotics remain the cornerstone in the treatment of CAP. However, two aspects seem to contribute to a worse outcome: an uncontrolled inflammatory reaction and an inadequate immune response. Adjuvant treatments, such as corticosteroids and intravenous immunoglobulins, have been proposed to counterbalance these effects. The use of corticosteroids in patients with severe CAP and a strong inflammatory reaction can reduce the time to clinical stability, the risk of treatment failure, and the risk of progression to acute respiratory distress syndrome. The administration of intravenous immunoglobulins seems to reinforce the immune response to the infection in particular in patients with inadequate levels of antibodies and when an enriched IgM preparation has been used; however, more studies are needed to determinate their impact on outcome and to define the population that will receive more benefit.

The purpose of this study was to establish the microbial aetiology and outcomes of patients with community-acquired pneumonia (CAP) treated as outpatients after presenting to a hospital emergency care unit. A prospective observational study was carried out in the Hospital Clinic of Barcelona (Barcelona, Spain). All consecutive cases of CAP treated as outpatients were included. 568 adult outpatients with CAP were studied (mean ± SD age 47.2 ± 17.6 yrs; 110 (19.4%) were aged ≥ 65 yrs). Aetiological diagnoses were established in 188 (33.1%) cases. Streptococcus pneumoniae was the most frequent pathogen followed by Mycoplasma pneumoniae and respiratory viruses. Legionella was detected in 13 (2.3%) cases. More than one causative agent was found in 17 (9.0%) patients. Mortality was low (three (0.5%) patients died) and other adverse events were rare (30 (5.2%) patients had complications, 13 (2.3%) were re-admitted and treatment failed in 13 (2.3%)). Complications were mostly related to pleural effusion and empyema, and re-admissions and treatment failures to comorbidities. Outpatients with CAP have a characteristic microbial pattern. Regular antipneumococcal coverage remains mandatory. Treatment failures and re-admissions are rare and may be reduced by increased attention to patients requiring short-term observation in the emergency care unit and in the presence of pleural effusion and comorbidities.

A patient with 2 weeks of breathlessness during daily activities and intense pain in the right shoulder was referred for physiological evaluation. A chest radiograph showed new right hemidiaphragm elevation, pulmonary function tests demonstrated reduced lung volumes, and maximum inspiratory pressure was markedly reduced. Additional testing based on an understanding of the structure, function, and innervation of the diaphragm confirmed the diagnosis.

Impairment of (inspiratory and expiratory) respiratory muscles is a common clinical finding, not only in patients with neuromuscular disease but also in patients with primary disease of the lung parenchyma or airways. Although such impairment is common, its recognition is usually delayed because its signs and symptoms are nonspecific and late. This delayed recognition, or even the lack thereof, occurs because the diagnostic tests used in the assessment of respiratory muscle strength are not widely known and available. There are various methods of assessing respiratory muscle strength during the inspiratory and expiratory phases. These methods are divided into two categories: volitional tests (which require patient understanding and cooperation); and non-volitional tests. Volitional tests, such as those that measure maximal inspiratory and expiratory pressures, are the most commonly used because they are readily available. Non-volitional tests depend on magnetic stimulation of the phrenic nerve accompanied by the measurement of inspiratory mouth pressure, inspiratory esophageal pressure, or inspiratory transdiaphragmatic pressure. Another method that has come to be widely used is ultrasound imaging of the diaphragm. We believe that pulmonologists involved in the care of patients with respiratory diseases should be familiar with the tests used in order to assess respiratory muscle function.Therefore, the aim of the present article is to describe the advantages, disadvantages, procedures, and clinical applicability of the main tests used in the assessment of respiratory muscle strength.

Background: Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission.Methods: This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission.Results: Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001).Conclusions: The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes.

Thrombocytosis, often considered a marker of normal inflammatory reaction of infections, has been recently associated with increased mortality in hospitalized patients with community-acquired pneumonia (CAP). We assessed the characteristics and outcomes of patients with CAP and thrombocytosis (platelet count ≥ 4 × 105/mm3) compared with thrombocytopenia (platelet countlt; 105/mm3) and normal platelet count.We prospectively analyzed 2,423 consecutive, hospitalized patients with CAP. We excluded patients with immunosuppression, neoplasm, active TB, or hematologic disease.Fifty-three patients (2%) presented with thrombocytopenia, 204 (8%) with thrombocytosis, and 2,166 (90%) had normal platelet counts. Patients with thrombocytosis were younger (Plt; .001); those with thrombocytopenia more frequently had chronic heart and liver disease (Plt; .001 for both). Patients with thrombocytosis presented more frequently with respiratory complications, such as complicated pleural effusion and empyema (Plt; .001), whereas those with thrombocytopenia presented more often with severe sepsis (Plt; .001), septic shock (P = .009), need for invasive mechanical ventilation (Plt; .001), and ICU admission (P = .011). Patients with thrombocytosis and patients with thrombocytopenia had longer hospital stays (P = .004), and higher 30-day mortality (P = .001) and readmission rates (P = .011) than those with normal platelet counts. Multivariate analysis confirmed a significant association between thrombocytosis and 30-day mortality (OR, 2.720; 95% CI, 1.589-4.657; Plt; .001). Adding thrombocytosis to the confusion, respiratory rate, and BP plus age ≥65 years score slightly improved the accuracy to predict mortality (area under the receiver operating characteristic curve increased from 0.634 to 0.654, P = .049).Thrombocytosis in patients with CAP is associated with poor outcome, complicated pleural effusion, and empyema. The presence of thrombocytosis in CAP should encourage ruling out respiratory complication and could be considered for severity evaluation.

Primary biliary cirrhosis (PBC), which is characterised by progressive destruction of intrahepatic bile ducts, is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies. The prognosis of the disease has improved due to both the recognition of earlier and indolent cases, and to the wide use of ursodeoxycholic acid (UDCA). New indicators of prognosis are available that will be useful especially for the growing number of patients with less severe disease. Most patients are asymptomatic at presentation. Pruritus may represent the most distressing symptom and, when UDCA is ineffective, cholestyramine represents the mainstay of treatment. Complications of long-standing cholestasis may be clinically relevant only in very advanced stages. Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while, in advanced stages, the only therapeutic option remains liver transplantation.

BACKGROUND: The burden of pneumococcal disease is measured only through patients with invasive pneumococcal disease. The urinary antigen test (UAT) for pneumococcus has exhibited high sensitivity and specificity. We aimed to compare the pneumococcal pneumonias diagnosed as invasive disease with pneumococcal pneumonias defined by UAT results. METHODS: A prospective observational study of consecutive nonimmunosuppressed patients with community-acquired pneumonia was performed from January 2000 to December 2014. Patients were stratified into two groups: invasive pneumococcal pneumonia (IPP) defined as a positive blood culture or pleural fluid culture result and noninvasive pneumococcal pneumonia (NIPP) defined as a positive UAT result with negative blood or pleural fluid culture result. RESULTS: We analyzed 779 patients (15%) of 5,132, where 361 (46%) had IPP and 418 (54%) had NIPP. Compared with the patients with IPP, those with NIPP presented more frequent chronic pulmonary disease and received previous antibiotics more frequently. Patients with IPP presented more severe community-acquired pneumonia, higher levels of inflammatory markers, and worse oxygenation at admission; more pulmonary complications; greater extrapulmonary complications; longer time to clinical stability; and longer length of hospital stay compared with the NIPP group. Age, chronic liver disease, mechanical ventilation, and acute renal failure were independent risk factors for 30-day crude mortality. Neither IPP nor NIPP was an independent risk factor for 30-day mortality. CONCLUSIONS: A high percentage of confirmed pneumococcal pneumonia is diagnosed by UAT. Despite differences in clinical characteristics and outcomes, IPP is not an independent risk factor for 30-day mortality compared with NIPP, reinforcing the importance of NIPP for pneumococcal pneumonia.