A pneumococcal pneumonia and influenza vaccination quality improvement program for women receiving chemotherapy for gynecologic cancers at a major tertiary cancer Centre.

OBJECTIVE: International guidelines recommend pneumococcal pneumonia and influenza vaccination for all patients with solid organ malignancies prior to initiating chemotherapy. Baseline vaccination rates (March 2019) for pneumococcal pneumonia and influenza at our tertiary cancer centre were 8% and 40%, respectively. The aim of this study was to increase the number of gynecologic chemotherapy patients receiving pneumococcal and influenza vaccinations to 80% by March 2020. METHODS: We performed an interrupted time series study using structured quality improvement methodology. Three interventions were introduced to address vaccination barriers: an in-house vaccination program, a staff education campaign, and a patient care bundle (pre-printed prescription, information brochure, vaccine record booklet). Process and outcome data were collected by patient survey and pharmacy audit and analyzed on statistical process control charts. RESULTS: We identified 195 eligible patients. Pneumococcal and influenza vaccination rates rose significantly from 5% to a monthly mean of 61% and from 36% to a monthly mean of 67%, respectively. The 80% target was reached for both vaccines during one or more months of study. The in-house vaccination and staff education programs were major contributors to the improvement, whereas the information brochure and record booklet were minor contributors. CONCLUSIONS: Three interventions to promote pneumococcal and influenza vaccination among chemotherapy patients resulted in significantly improved vaccination rates. Lessons learned about promoting vaccine uptake may be generalizable to different populations and vaccine types. In response to the global COVID-19 pandemic, initiatives to expand the program to all chemotherapy patients at our centre are underway.

Effect of CARD9 Deficiency on Neutrophil-Mediated Host Defense against Pulmonary Infection with Streptococcus pneumoniae.

Streptococcus pneumoniae is a major causative bacterium of community-acquired pneumonia. Dendritic cell-associated C-type lectin-2 (dectin-2), one of the C-type lectin receptors (CLRs), was previously reported to play a pivotal role in host defense against pneumococcal infection through regulating phagocytosis by neutrophils while not being involved in neutrophil accumulation. In the present study, to elucidate the possible contribution of other CLRs to neutrophil accumulation, we examined the role of caspase recruitment domain-containing protein 9 (CARD9), a common adaptor molecule for signal transduction triggered by CLRs, in neutrophilic inflammatory response against pneumococcal infection. Wild-type (WT), CARD9 knockout (KO), and dectin-2 KO mice were infected intratracheally with pneumococcus, and the infected lungs were histopathologically analyzed to assess neutrophil accumulation at 24 h postinfection. Bronchoalveolar lavage fluids (BALFs) were collected at the same time point to count the neutrophils and assess the production of inflammatory cytokines and chemokines. Neutrophil accumulation was significantly decreased in CARD9 KO mice, but not in dectin-2 KO mice. Tumor necrosis factor alpha (TNF-α), keratinocyte-derived chemokine (KC), and macrophage inflammatory protein-2 (MIP-2) production in BALFs were also attenuated in CARD9 KO mice, but not in dectin-2 KO mice. Production of TNF-α and KC by alveolar macrophages stimulated with pneumococcal culture supernatants was significantly attenuated in CARD9 KO mice, but not in dectin-2 KO mice, compared to that in each group's respective control mice. In addition, pneumococcus-infected CARD9 KO mice showed larger bacterial burdens in the lungs than did WT mice. These data indicate that CARD9 is required for neutrophil migration after pneumococcal infection, as well as inflammatory cytokine and chemokine production by alveolar macrophages, and suggest that a CLR distinct from dectin-2 may be involved in this response.

Plasma cytokine profile on admission related to aetiology in community-acquired pneumonia.

BACKGROUND: Potentially unnecessary antibiotic use for community-acquired pneumonia (CAP) contributes to selection of antibiotic-resistant pathogens. Cytokine expression at the time that treatment is started may assist in identifying patients not requiring antibiotics. We determined plasma cytokine patterns in patients retrospectively categorized as strict viral, pneumococcal or combined viral-bacterial CAP. OBJECTIVE: To investigate whether cytokine-based prediction models can be used to differentiate strict viral CAP from other aetiologies at admission. METHODS: From 344 hospitalized CAP patients, 104 patients were categorized as viral CAP (n = 17), pneumococcal CAP (n = 48) and combined bacterial-viral CAP (n = 39). IL-6, IL-10, IL-27, IFN-γ and C-reactive protein (CRP) were determined on admission in plasma. Prediction of strict viral aetiology was explored with two multivariate regression models and ROC curves. RESULTS: Viral pneumonia was predicted by logistic regression using multiple cytokine levels (IL-6, IL-27 and CRP) with an AUC of 0.911 (95% CI: 0.852-0.971, P < .001). For the same patients the AUC of CRP was 0.813 (95% CI: 0.728-0.898, P < .001). CONCLUSIONS: This study demonstrated differences in cytokine expression in selected CAP patients between viral and bacterial aetiology. Prospective validation studies are warranted.

Mucosal vaccine based on attenuated influenza virus and the group B Streptococcus recombinant peptides protected mice from influenza and S. pneumoniae infections.

Although many influenza-related deaths are attributable to secondary bacterial infection with S. pneumoniae, vaccines that simultaneously protect against influenza and pneumococcal infection are currently not developed. The aim of our study was to evaluate the possibility to prevent post-influenza pneumococcal infection using an associated vaccine based on live influenza vaccine (LAIV) combined with recombinant polypeptides derived from superficial factors of Group B streptococcus (GBS) determining pathogenicity. We demonstrated in a model of post-influenza pneumococcal pneumonia that intranasal pneumococcal super-infection seriously complicated the course of A/Shanghai/2/2013(H7N9) CDC-RG virus infection in mice. Associated immunization using LAIV and GBS vaccine (GBSV) prevented post-influenza pneumococcal pneumonia better than mono-LAIV or GBSV immunization. At the same time, parenteral pneumococcal post-influenza infection of immune mice was more severe in the groups immunized using recombinant GBS peptides which can be explained by antibody-dependent enhancement of infection. In this case, the introduction of blockers of histamine receptors type 1 and 2 reduced the burden of secondary pneumococcal infection.

Alcohol consumption increases susceptibility to pneumococcal pneumonia in a humanized murine HIV model mediated by intestinal dysbiosis.

Alcohol use in persons living with HIV (PLWH) worsens the severity of bacterial pneumonia. However, the exact mechanism(s) by which this occurs remain ill-defined. We hypothesized that alcohol in the setting of HIV infection decreases Streptococcus pneumoniae clearance from the lung through mechanisms mediated by the gut microbiota. Humanized BLT (bone marrow, liver, thymus) mice were infected with 1 × 104 TCID50 of HIV (BAL and JRCSF strains) via intraperitoneal (i.p.) injection. One week post-HIV infection, animals were switched to a Lieber-DeCarli 5% ethanol diet or an isocaloric control diet for 10 days. Alcohol-fed animals were also given two binges of 2 g/kg ethanol on days 5 and 10. Feces were also collected, banked, and the community structures were analyzed. Mice were then infected with 1 × 105 CFU (colony-forming units) of S. pneumoniae and were sacrificed 48 h later. HIV-infected mice had viral loads of ∼2 × 104 copies/mL of blood 1 week post-infection, and exhibited an ∼57% decrease in the number of circulating CD4+ T cells at the time of sacrifice. Fecal microbial community structure was significantly different in each of the feeding groups, as well as with HIV infection. Alcohol-fed mice had a significantly higher burden of S. pneumoniae 48 h post-infection, regardless of HIV status. In follow-up experiments, female C57BL/6 mice were treated with a cocktail of antibiotics daily for 2 weeks and recolonized by gavage with intestinal microbiota from HIV+ ethanol-fed, HIV+ pair-fed, HIV- ethanol-fed, or HIV- pair-fed mice. Recolonized mice were then infected with S. pneumoniae and were sacrificed 48 h later. The intestinal microbiota from alcohol-fed mice (regardless of HIV status) significantly impaired clearance of S. pneumoniae. Collectively, these data indicate that alcohol feeding, as well as alcohol-associated intestinal dysbiosis, compromise pulmonary host defenses against pneumococcal pneumonia. Determining whether HIV infection acts synergistically with alcohol use in impairing pulmonary host defenses will require additional study.

Invasive and Complicated Pneumococcal Infection in Patients with Cancer.

BACKGROUND: In susceptible patients, Streptococcus pneumoniae can cause complicated pneumonia and invasive pneumococcal disease. The aim of this study was to assess the clinical and antimicrobial features of complicated and invasive pneumococcal disease in patients with cancer. METHODS: We conducted a retrospective study including all S. pneumoniae isolates between January 1, 2007 and December 31, 2015 in an oncology center. Capsular serotyping was done in isolates from sterile sites. RESULTS: There were 103 episodes: 69 with invasive pneumococcal disease and 34 with complicated pneumonia. Sixty-two patients were male (60%); mean age was 50 years. Eighty-four isolates were susceptible to penicillin (81.6%), 11 (10%) were intermediate, and eight (8.3%) were resistant. Serotyping was performed in 64 isolates; the main serotypes identified were 3 (n = 13) and 19A (n = 11). No patient had a record of vaccination. Mortality at seven days attributed to pneumococcal infection was different in invasive pneumococcal disease (n = 18, 28.6%) vs. pneumonia (n = 3, 8.9%; p = 0.04). Thirty-day mortality related with the infectious process was statistically different between both groups: 21 patients with invasive pneumococcal disease (30.4%) and six with pneumonia (17.6%; p = 0.04). By logistic analysis, the risk factor associated with mortality was not having received appropriate antimicrobial treatment in the first 48 hours. CONCLUSIONS: S. pneumoniae is a pathogen related with high mortality in patients with cancer. Pneumococcal immunization needs to be reinforced in this population.

Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice.

Protecting the integrity of the lung epithelial barrier is essential to ensure respiration and proper oxygenation in patients suffering from various types of lung inflammation. Type I interferon (IFN-I) has been associated with pulmonary epithelial barrier function, however, the mechanisms and involved cell types remain unknown. We aimed to investigate the importance of IFN-I with respect to its epithelial barrier strengthening function to better understand immune-modulating effects in the lung with potential medical implications. Using a mouse model of pneumococcal pneumonia, we revealed that IFN-I selectively protects alveolar epithelial type II cells (AECII) from inflammation-induced cell death. Mechanistically, signaling via the IFN-I receptor on AECII is sufficient to promote AECII survival. The net effects of IFN-I are barrier protection, together with diminished tissue damage, inflammation, and bacterial loads. Importantly, we found that the protective role of IFN-I can also apply to sterile acute lung injury, in which loss of IFN-I signaling leads to a significant reduction in barrier function caused by AECII cell death. Our data suggest that IFN-I is an important mediator in lung inflammation that plays a protective role by antagonizing inflammation-associated cell obstruction, thereby strengthening the integrity of the epithelial barrier.

Preventative Care in the Patient with Inflammatory Bowel Disease: What Is New?

Patients with inflammatory bowel disease (IBD) do not receive routine preventative care at the same rate as general medical patients. This patient population is at increased risk of vaccine preventable illness such as influenza and pneumococcal pneumonia. This review will discuss health maintenance needs and preventative care issues in patients with IBD.

Proteasome ß5i Subunit Deficiency Affects Opsonin Synthesis and Aggravates Pneumococcal Pneumonia.

Immunoproteasomes, harboring the active site subunits ß5i/LMP7, ß1i/LMP2, and ß2i/MECL1 exert protective, regulatory or modulating functions during infection-induced immune responses. Immunoproteasomes are constitutively expressed in hematopoietic derived cells, constituting the first line of defense against invading pathogens. To clarify the impact of immunoproteasomes on the innate immune response against Streptococcus pneumoniae, we characterized the progression of disease and analyzed the systemic immune response in ß5i/LMP7-/- mice. Our data show that ß5i/LMP7 deficiency, which affected the subunit composition of proteasomes in murine macrophages and liver, was accompanied by reduced transcription of genes encoding immune modulating molecules such as pentraxins, ficolins, and collectins. The diminished opsonin expression suggested an impaired humoral immune response against invading pneumococci resulting in an aggravated systemic dissemination of S. pneumoniae in ß5i/LMP7-/- mice. The impaired bacterial elimination in ß5i/LMP7-/- mice was accompanied by an aggravated course of pneumonia with early mortality as a consequence of critical illness during the late phase of disease. In summary our results highlight an unsuspected role for immuno-subunits in modulating the innate immune response to extracellular bacterial infections.

Preventing Infections in Sickle Cell Disease: The Unfinished Business.

While encapsulated bacterial agents, particularly Streptococcus pneumoniae, are recognized as important microbes that are associated with serious illness in hosts with sickle cell disease (SCD), multiple pathogens are implicated in infectious manifestations of SCD. Variations in clinical practice have been an obstacle to the universal implementation of infection preventive management through active, targeted vaccination of these individuals and routine usage of antibiotic prophylaxis. Paradoxically, in low-income settings, there is evidence that SCD also increases the risk for several other infections that warrant additional infection preventive measures. The infection preventive care among patients with SCD in developed countries does not easily translate to the adoption of these recommendations globally, which must take into account the local epidemiology of infections, available vaccines and population-specific vaccine efficacy, environment, health care behaviors, and cultural beliefs, as these are all factors that play a complex role in the manifestation of SCD and the prevention of infectious disease morbidity.

Which individuals are at increased risk of pneumococcal disease and why? Impact of COPD, asthma, smoking, diabetes, and/or chronic heart disease on community-acquired pneumonia and invasive pneumococcal disease.

Pneumococcal disease (including community-acquired pneumonia and invasive pneumococcal disease) poses a burden to the community all year round, especially in those with chronic underlying conditions. Individuals with COPD, asthma or who smoke, and those with chronic heart disease or diabetes mellitus have been shown to be at increased risk of pneumococcal disease compared with those without these risk factors. These conditions, and smoking, can also adversely affect patient outcomes, including short-term and long-term mortality rates, following pneumonia. Community-acquired pneumonia, and in particular pneumococcal pneumonia, is associated with a significant economic burden, especially in those who are hospitalised, and also has an impact on a patient's quality of life. Therefore, physicians should target individuals with COPD, asthma, heart disease or diabetes mellitus, and those who smoke, for pneumococcal vaccination at the earliest opportunity at any time of the year.

Pneumococcal vaccine and patients with pulmonary diseases.

Chronic pulmonary diseases are chronic diseases that affect the airways and lung parenchyma. Examples of common chronic pulmonary diseases include asthma, bronchiectasis, chronic obstructive lung disease, lung fibrosis, sarcoidosis, pulmonary hypertension, and cor pulmonale. Pulmonary infection is considered a significant cause of mortality in patients with chronic pulmonary diseases. Streptococcus pneumoniae is the leading isolated bacteria from adult patients with community-acquired pneumonia, the most common pulmonary infection. Vaccination against S. pneumoniae can reduce the risk of mortality, especially from more serious infections in both immunocompetent and immunocompromised patients. Patients with chronic pulmonary diseases who take steroids or immunomodulating therapy (eg, methotrexate, anti-tumor necrosis factor inhibitors), or who have concurrent sickle cell disease or other hemoglobinopathies, primary immunodeficiency disorders, human immunodeficiency virus infection/acquired immunodeficiency syndrome, nephrotic syndrome, and hematologic or solid malignancies should be vaccinated with both 13-valent pneumococcal conjugate vaccine and the pneumococcal polysaccharide vaccine 23-valent.

Smoking and alcohol abuse are the most preventable risk factors for invasive pneumonia and other pneumococcal infections.

OBJECTIVES: To determine the prevalence of smoking and alcohol abuse among patients with invasive pneumococcal disease (IPD) in order to promote prevention strategies. METHODS: We prospectively studied all culture-proven IPD cases in patients aged ≥ 18 years during the period 1997-2011. The habits of smoking and alcohol abuse were evaluated. Pneumococcal serotyping was performed. RESULTS: There were 1378 IPD cases, with a mean age of 61 ± 17 years; 65% were males. Compared to the general population aged 18-64 years, patients with IPD of the same age group were more often current smokers (57% vs. 35%, p < 0.001) and alcohol abusers (21% vs. 6%, p < 0.001). Among patients with IPD, young adults (aged 18-49 vs. 50-64 vs. ≥ 65 years) were more commonly current smokers (71% vs. 40% vs.14%, p < 0.001) and alcohol abusers (23% vs. 18% vs. 6%, p < 0.001). Males were more frequently smokers and alcohol abusers than females. Smokers and alcohol abusers more often had underlying diseases such as HIV infection and chronic liver disease. Pneumonia was more common in smokers and peritonitis in alcohol abusers. Alcohol abuse conferred higher mortality. Certain pneumococcal serotypes, such as serotypes 1, 8, and 23F, more frequently caused IPD in smokers, and serotypes 4, 11A, and 19F in alcohol abusers. CONCLUSIONS: Smoking and alcohol abuse are the most preventable risk factors for IPD. Implementing smoking and alcohol abuse cessation programs and a pneumococcal vaccination schedule are essential to diminish the burden of pneumonia and other pneumococcal infections.

Community-acquired pneumonia among smokers.

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.

Linezolid decreases susceptibility to secondary bacterial pneumonia postinfluenza infection in mice through its effects on IFN-γ.

Influenza infection predisposes patients to secondary bacterial pneumonia that contributes significantly to morbidity and mortality. Although this association is well documented, the mechanisms that govern this synergism are poorly understood. A window of hyporesponsiveness following influenza infection has been associated with a substantial increase in local and systemic IFN-γ concentrations. Recent data suggest that the oxazolidinone antibiotic linezolid decreases IFN-γ and TNF-α production in vitro from stimulated PBMCs. We therefore sought to determine whether linezolid would reverse immune hyporesponsiveness after influenza infection in mice through its effects on IFN-γ. In vivo dose-response studies demonstrated that oral linezolid administration sufficiently decreased bronchoalveolar lavage fluid levels of IFN-γ at day 7 postinfluenza infection in a dose-dependent manner. The drug also decreased morbidity as measured by weight loss compared with vehicle-treated controls. When mice were challenged intranasally with Streptococcus pneumoniae 7 d postinfection with influenza, linezolid pretreatment led to decreased IFN-γ and TNF-α production, decreased weight loss, and lower bacterial burdens at 24 h postbacterial infection in comparison with vehicle-treated controls. To determine whether these effects were due to suppression of IFN-γ, linezolid-treated animals were given intranasal instillations of rIFN-γ before challenge with S. pneumoniae. This partially reversed the protective effects observed in the linezolid-treated mice, suggesting that the modulatory effects of linezolid are mediated partially by its ability to blunt IFN-γ production. These results suggest that IFN-γ, and potentially TNF-α, may be useful drug targets for prophylaxis against secondary bacterial pneumonia following influenza infection.

Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes.

Macrophages play a key role in responding to pathogens and initiate an inflammatory response to combat microbe multiplication. Deactivation of macrophages facilitates resolution of the inflammatory response. Deactivated macrophages are characterized by an immunosuppressive phenotype, but the lack of unique markers that can reliably identify these cells explains the poorly defined biological role of this macrophage subset. We identified lipocalin 2 (LCN2) as both a marker of deactivated macrophages and a macrophage deactivator. We show that LCN2 attenuated the early inflammatory response and impaired bacterial clearance, leading to impaired survival of mice suffering from pneumococcal pneumonia. LCN2 induced IL-10 formation by macrophages, skewing macrophage polarization in a STAT3-dependent manner. Pulmonary LCN2 levels were tremendously elevated during bacterial pneumonia in humans, and high LCN2 levels were indicative of a detrimental outcome from pneumonia with Gram-positive bacteria. Our data emphasize the importance of macrophage deactivation for the outcome of pneumococcal infections and highlight the role of LCN2 and IL-10 as determinants of macrophage performance in the respiratory tract.

Etiology and factors contributing to the severity and mortality of community-acquired pneumonia.

OBJECTIVE: Community-acquired pneumonia (CAP) remains a major cause of death. No studies have reported the use of rapid influenza diagnostic tests (RIDT) for the etiological diagnosis, and the factors contributing to severity and mortality have not yet been fully investigated. The aim of this study was to review the etiologies of CAP using RIDT and to identify risk factors related to the severity and mortality of the disease. METHODS: This retrospective study assessed these factors in hospitalized patients, with special emphasis on microbial etiology. RESULTS: A total of 1,032 patients aged 63.9±18.3 years were studied, 66.2% of whom were men. Microbial identification was obtained in 57.0% of the cases. The most frequent causative microbial agents were Streptococcus pneumoniae, Mycoplasma pneumoniae and the influenza virus, and the second most frequent pathogens in the patients with severe CAP and the non-survivors were S. pneumoniae and the influenza virus. Age (≥65 years), chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, dementia and Legionella spp. infection and polymicrobial infection were each found to be independent factors related to severity in the multivariate analysis, whereas "unidentified pathogen" was found to be an independent factor for non-severe CAP. Age (≥65 years), chronic pulmonary aspergillosis, post-lung cancer surgery and severe CAP were found to be independent factors for non-survival according to a multivariate analysis. CONCLUSION: In addition to S. pneumoniae, the influenza virus was a frequent cause of CAP overall and a frequent causative pathogen in both severe cases of CAP and non-survivors. Legionella spp. infection and polymicrobial infection were found to be an independent factor for the severity of CAP along with advanced age and certain comorbidities. An advanced age, certain respiratory comorbidities and severe CAP were found to be important independent factors for the mortality of CAP.

Role of p38 mitogen-activated protein kinase in posttraumatic immunosuppression in mice.

BACKGROUND: Patients with multiple injuries surviving the initial insult are highly susceptible to secondary pneumonia, frequently progressing into sepsis and multiorgan failure. However, the underlying mechanisms of posttraumatic immunosuppression are poorly understood. We hypothesized that dysregulated p38 mitogen-activated protein kinase (MAPK) signaling accounts for impaired lung protective immunity in a model of trauma/hemorrhage (T/H) and subsequent pneumococcal pneumonia in mice. METHODS: C57BL6/N mice were subjected to trauma by midline laparotomy, and T/H was induced by midline laparotomy followed by cannulation of femoral arteries and veins to induce hemorrhage. Subsequently, mice were infected with Streptococcus pneumoniae. In selected experiments, mice were treated with a p38 MAPK inhibitor or vehicle control immediately after induction of T/H. RESULTS: Mice subjected to T/H showed significantly increased p38 MAPK activation in their lungs, which was accompanied by a reduced Escherichia coli phagocytosis by macrophages from T/H mice in vitro and an impaired pneumococcal killing activity of T/H mice in vivo, overall resulting in increased mortality of T/H mice after infection with S. pneumoniae. Application of p38 MAPK inhibitor BIRB796 immediately after T/H induction improved the bacterial phagocytosis activity of macrophages from T/H mice in vitro and lung pneumococcal killing in vivo but did not improve the survival of T/H mice challenged with S. pneumoniae. CONCLUSION: T/H triggers sustained p38 MAPK activation in the lungs of mice, which attenuates lung macrophage antibacterial activities and renders mice more susceptible to pneumococcal pneumonia. However, no major role for dysregulated p38 MAPK to affect survival of T/H mice after pneumococcal challenge was detected, suggesting that dysregulated p38 MAPK activity may possibly play only a limited role in posttraumatic immunosuppression in mice.

Increased mortality from infectious pneumonia after occupational exposure to inorganic dust, metal fumes and chemicals.

OBJECTIVES: There are epidemiological studies indicating that exposure to metal fumes is a risk factor for infectious pneumonia. Whether occupational exposure to other agents, such as inorganic dust or chemicals, also increases the risk for infectious pneumonia is not clear. The aim of the present study was to elucidate whether occupational exposure to respiratory pollutants and irritants increases the risk for infectious pneumonia. DESIGN: Prospective cohort study. Setting Swedish male construction workers. Participants 320,143 male construction workers exposed to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), wood dust, metal fumes and chemicals (organic solvents, diisocyanates and epoxi resins) or unexposed. Main outcome measures The cohort was followed from 1971 to 2003 and the main outcome measures were mortality to infectious pneumonia, lobar pneumonia or pneumococcal pneumonia. RRs were obtained by the person-years method and from Poisson regression models, adjusting for baseline values of age and smoking habits. RESULTS: Among men aged 20-64 years there was increased mortality from infectious pneumonias among construction workers exposed to metal fumes (RR 2.31, 95% CI 1.35 to 3.95), inorganic dust (RR 1.87, 95% CI 1.22 to 2.87) and chemicals (RR 1.91, 95% CI 1.37 to 3.22). The mortality was also increased from both lobar pneumonia and pneumococcal pneumonia. Among men aged 65-84 years the occupational exposure to inorganic dust and chemicals was associated with slightly increased mortality from infectious pneumonia. Among groups with mutually exclusive exposures there was increased mortality from infectious pneumonias among construction workers exposed to inorganic dust, but not among those exposed to wood dust or chemicals. There were no cases among workers exposed only to metal fumes. CONCLUSIONS: Our findings indicate that exposure to inorganic dust increases the mortality from infectious pneumonias, especially lobar pneumonia and pneumococcal pneumonia. The mechanism is unclear, but the effect may be mediated through induced airways inflammation.

[Does pulmonary contusion expose to the risk of Streptococcus pneumoniae infections? Results of an experimental study]. / La contusion pulmonaire expose-t-elle au risque de prolifération bactérienne à pneumocoque ? Résultats d'une étude expérimentale.

OBJECTIVE: To create a reliable and reproducible model of pulmonary contusion (PC) in rats in order to evaluate the influence of PC on bacterial lung proliferation. STUDY DESIGN: Experimental. ANIMALS: Male albino CD rats. METHODS: Animals were anesthetized and a PC was performed using a spring-loaded metal bar. The existence of an isolated right PC was confirmed by macroscopic, histological and radiological analysis. This model was used to compare four randomized groups of animals. These were either injured or only anesthetized and inoculated with a pneumococcal solution concentrated in 2 or 4 log(CFU/mL). The animals' lungs were collected for microbiological culture at 24 hours. The bacterial count evolution per gram of lung was the primary endpoint. RESULTS: Twelve rats were needed to validate the model, 84 to determine the morbidity and mortality and its reproducibility and 66 to assess the intra-pulmonary bacterial proliferation. The PC obtained was unilateral and isolated in 95% of cases. Mortality rate was 43%. For a low initial inoculum concentration (2 log [CFU/mL]), there is bacterial overgrowth in the PC group versus the no-PC group (P=0.0017). This difference was not found when the inoculum was more concentrated. CONCLUSION: This experimental model is reliable and reproducible. The initially high mortality seems to decrease with the experience of operators. The CP significantly increases intra-pulmonary bacterial proliferation when the inoculation is low. A high inoculum neutralizes the effect of CP. These results suggest that enhanced prevention of micro-inhalation could be beneficial in cases of CP.