Bronchopulmonary Infections Research Articles

Effective control of Staphylococcus aureus lung infection despite tertiary lymphoid structure disorganisation.

Tertiary lymphoid structures (TLS) are triggered by persistent bronchopulmonary infection with Staphylococcus aureus, but their roles remain elusive. The present study sought to examine the effects of B- and/or T-cell depletion on S. aureus infection and TLS development (lymphoid neogenesis) in mice. C57Bl/6 mice were pre-treated with 1) an anti-CD20 monoclonal antibody (mAb) (B-cell depletion) or 2) an anti-CD4 and/or an anti-CD8 mAb (T-cell depletion) or 3) a combination of anti-CD20, anti-CD4 and anti-CD8 mAbs (combined B- and T-cell depletion) or 4) isotype control mAbs. After lymphocyte depletion, mice were infected by intratracheal instillation of agarose beads containing S. aureus (106 CFU per mouse). 14 days later, bacterial load and lung inflammatory cell infiltration were assessed by cultures and immunohistochemistry, respectively. 14 days after S. aureus-bead instillation, lung bacterial load was comparable between control and lymphocyte-depleted mice. While TLS were observed in the lungs of infected mice pre-treated with control mAbs, these structures were disorganised or abolished in the lungs of lymphocyte-depleted mice. The absence of CD20+ B-lymphocytes had no effect on CD3+ T-lymphocyte infiltration, whereas CD4+/CD8+ T-cell depletion markedly reduced CD20+ B-cell infiltration. Depletion of CD4+ or CD8+ T-cells separately had limited effect on B-cell infiltration, but led to the absence of germinal centres. TLS disorganisation is not associated with loss of infection control in mice persistently infected with S. aureus.

Effect of nutritional support in patients with lower respiratory tract infection: Secondary analysis of a randomized clinical trial

BackgroundIn polymorbid patients with bronchopulmonary infection, malnutrition is an independent risk factor for mortality. There is a lack of interventional data investigating whether providing nutritional support during the hospital stay in patients at risk for malnutrition presenting with lower respiratory tract infection lowers mortality.MethodsFor this secondary analysis of a randomized clinical trial (EFFORT), we analyzed data of a subgroup of patients with confirmed lower respiratory tract infection from an initial cohort of 2028 patients. Patients at nutritional risk (Nutritional Risk Screening [NRS] score ≥3 points) were randomized to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). The primary endpoint of this analysis was all-cause 30-day mortality.ResultsWe included 378 of 2028 EFFORT patients (mean age 74.4 years, 24% with COPD) into this analysis. Compared to usual care hospital nutrition, individualized nutritional support to reach caloric and protein goals showed a similar beneficial effect of on the risk of mortality in the subgroup of respiratory tract infection patients as compared to the main EFFORT trial (odds ratio 0.47 [95%CI 0.17 to 1.27, p = 0.136] vs 0.65 [95%CI 0.47 to 0.91, p = 0.011]) with no evidence of a subgroup effect (p for interaction 0.859). Effects were also similar among different subgroups based on etiology and type of respiratory tract infection and for other secondary endpoints.ConclusionThis subgroup analysis from a large nutrition support trial suggests that patients at nutritional risk as assessed by NRS 2002 presenting with bronchopulmonary infection to the hospital likely have a mortality benefit from individualized inhospital nutritional support. The small sample size and limited statistical power calls for larger nutritional studies focusing on this highly vulnerable patient population.Clinical trial registrationRegistered under ClinicalTrials.gov Identifier no. NCT02517476.

Biophysical and In-Silico Studies of Phytochemicals Targeting Chorismate Synthase from Drug-Resistant Moraxella Catarrhalis

Chorismate serves as a crucial precursor for the synthesis of many aromatic compounds essential for the survival and virulence in various bacteria and protozoans. Chorismate synthase, a vital enzyme in the shikimate pathway, is responsible for the formation of chorismate from enolpyruvylshikimate-3-phosphate (EPSP). Moraxella catarrhalis is reported to be resistant to many beta-lactam antibiotics and causes chronic ailments such as otitis media, sinusitis, laryngitis, and bronchopulmonary infections. Here, we have cloned the aroC gene from Moraxella catarrhalis in pET28c and heterologously produced the chorismate synthase (~ 43kDa) in Escherichia coli BL21(DE3) cells. We have predicted the three-dimensional structure of this enzyme and used the refined model for ligand-based virtual screening against Supernatural Database using PyRx tool that led to the identification of the top three molecules (caffeic acid, gallic acid, and o-coumaric acid). The resultant protein-ligand complex structures were subjected to 50ns molecular dynamics (MD) simulation using GROMACS. Further, the binding energy was calculated by MM/PBSA approach using the trajectory obtained from MD simulation. The binding affinities of these compounds were validated with ITC experiments, which suggest that gallic acid has the highest binding affinity amongst these three phytochemicals. Together, these results pave the way for the use of these phytochemicals as potential anti-bacterial compounds.

VANISHING LUNGS IN SARCOID DISEASE

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Sarcoidosis is a multi-system disease with an unclear etiology that is characterized by non-caseating granulomas, T lymphocytes and mononuclear phagocytes in involved tissues. Hilar adenopathy is the most common initial manifestation with bullous emphysema being more of a rare outcome with an aggressive course. CASE PRESENTATION: A 39-year-old male smoker presented with recurrent bronchopulmonary infections. He had been prescribed steroids and antibiotics with interval improvement in the past. The patient endorsed shortness of breath on exertion with wheezing and a productive cough with clear phlegm. Vital signs and spot pulse oximetry were within normal range. A physical examination revealed decreased breath sounds throughout all lung fields as well as prolonged expiratory phase however no added sounds were appreciated. Laboratory values were within normal limit. Initial chest x-ray showed hilar adenopathy and follow up computed tomography (CT) scan showed chronic pulmonary nodularity with coalescent regions, predominantly affecting the upper lobes and superior segments of the lower lobes with mediastinal hilar lymphadenopathy. Pulmonary Function Test (PFT) showed severe obstructive disease and hyperinflation with air trapping. He subsequently underwent bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy. Tissue pathology showed non-caseating granulomatous inflammation confirming sarcoidosis. He was started on oral prednisone with minimal improvement and maximal inhaler therapy was added with initial improvement however later, his symptoms progressed, and he suffered significant decline in lung capacity. The 1 year follow up CT scan revealed early emphysematous changes that progressed quickly over the course of 3 years into severe emphysema and he eventually required supplemental oxygen. DISCUSSION: The bullous form of sarcoidosis was first reported in 1949. The etiology of emphysema is thought to be related to the obstruction of bronchioles from extrinsic pressure due to lymphadenopathy and endobronchial disease, causing peripheral air trapping and alveolar distention. Cavitary lung disease in sarcoidosis may form as a result of infection however true primary cavities formed by sarcoid granulomas of the walls are extremely rare. Most patients had been noted to have bullous changes within 3–4 years of symptom development. The diagnosis of emphysema is made from radiographic appearance, in addition to a decrease in diffusing capacity and lung volumes. Treatment is primarily medical, consisting of corticosteroids and immunosuppressive agents. Bullectomies are performed if disease is localized. In severe disease, lung transplantation is performed as a final option. CONCLUSIONS: Clinicians should be aware of progressive sarcoid with underlying emphysema as managing this group of patients can be particularly challenging given the aggressive nature of the disease. Reference #1: Jeebun V, Forrest IA. Sarcoidosis: An under-recognised cause for bullous lung disease? Eur Respir J. 2009;34(4):999-1001. doi:10.1183/09031936.00084609 Reference #2: Burke RM. Vanishing Lungs: A Case Report of Bullous Emphysema. Radiology. 1937;28(3):367-371. doi:10.1148/28.3.367 Reference #3: Miller A. The vanishing lung syndrome associated with pulmonary sarcoidosis. Br J Dis Chest. 1981;75(2):209-214. DISCLOSURES: No relevant relationships by Mohammed Al-Ourani, source=Web Response No relevant relationships by Yasmeen Obeidat, source=Web Response No relevant relationships by Batarseh Rami, source=Admin input

Effectiveness of expiratory flow acceleration in patients with Parkinson's disease and swallowing deficiency: A preliminary study

ObjectivesParkinson's disease (PD) causes dysfunction both to swallowing and to the cough mechanism. Oropharyngeal dysphagia is the main cause of pneumonia, due to silent aspiration of food and saliva. Pneumonia is the leading cause of death in PD. Different strategies exist to reduce the risk of inhalation and associated lung infections, but evidence of their efficacy is still unclear. The aim of this preliminary study was to investigate if adding an expiratory flow acceleration (EFA®) technique to standard therapy (ST) for dysphagia can reduce the incidence of bronchopulmonary infections and improve quality of life, respiratory function parameters, cough, and airways encumbrance perception. Materials and MethodsTwenty-five patients with PD were randomized to two groups: ST vs. ST + EFA. Patients were re-assessed at 30, 180 and 360 days from start of treatment. The primary outcome was the incidence of respiratory exacerbations together with quality of life score (PDQ-39). Secondary outcomes were changes in respiratory function tests, cough capacity (CPEF), perceived health status (Euro-QOL-VAS), cough, and upper airways encumbrance perception evaluated by visual numeric scale (VNS). ResultsTwenty patients concluded the study (10 each group). Albeit the difference was not significant, less respiratory infections, symptoms, hospital admissions and medical visits were found in the study group. Furthermore, there was a significant difference in cough effectiveness measured with the peak cough expiratory flow (PCEF) and other spirometry parameters (FEV1, FVC), and also in specific and generic health-related quality of life measures (PDQ-39, Euro-QoL-VAS). ConclusionThe results of this preliminary study support the use of EFA® technology in Parkinson's patients with dysphagia to reduce the risk of respiratory complications. Nevertheless, further studies are needed in a larger, more representative sample to definitively confirm the usefulness of this technique in PD patients.

Temperate Bacteriophages (Prophages) in Pseudomonas aeruginosa Isolates Belonging to the International Cystic Fibrosis Clone (CC274).

Bacteriophages are important in bacterial ecology and evolution. Pseudomonas aeruginosa is the most prevalent bacterial pathogen in chronic bronchopulmonary infection in cystic fibrosis (CF). In this study, we used bioinformatics, microbiological and microscopy techniques to analyze the bacteriophages present in 24 P. aeruginosa isolates belonging to the international CF clone (ST274-CC274). Interestingly, we detected the presence of five members of the Inoviridae family of prophages (Pf1, Pf4, Pf5, Pf6, Pf7), which have previously been observed in P. aeruginosa. In addition, we identified a new filamentous prophage, designated Pf8, in the P. aeruginosa AUS411.500 isolate belonging to the international CF clone. We detected only one prophage, never previously described, from the family Siphoviridiae (with 66 proteins and displaying homology with PHAGE_Pseudo_phi297_NC_016762). This prophage was isolated from the P. aeruginosa AUS531 isolate carrying a new gene which is implicated in the phage infection ability, named Bacteriophage Control Infection (bci). We characterized the role of the Bci protein in bacteriophage infection and in regulating the host Quorum Sensing (QS) system, motility and biofilm and pyocyanin production in the P. aeruginosa isogenic mutant AUS531Δbci isolate. The findings may be relevant for the identification of targets in the development of new strategies to control P. aeruginosa infections, particularly in CF patients.

Dissecting the antibacterial activity of oxadiazolone-core derivatives against Mycobacterium abscessus.

Mycobacterium abscessus (M. abscessus), a rapidly growing mycobacterium, is an emergent opportunistic pathogen responsible for chronic bronchopulmonary infections in individuals with respiratory diseases such as cystic fibrosis. Most treatments of M. abscessus pulmonary infections are poorly effective due to the intrinsic resistance of this bacteria against a broad range of antibiotics including anti-tuberculosis agents. Consequently, the number of drugs that are efficient against M. abscessus remains limited. In this context, 19 oxadiazolone (OX) derivatives have been investigated for their antibacterial activity against both the rough (R) and smooth (S) variants of M. abscessus. Several OXs impair extracellular M. abscessus growth with moderated minimal inhibitory concentrations (MIC), or act intracellularly by inhibiting M. abscessus growth inside infected macrophages with MIC values similar to those of imipenem. Such promising results prompted us to identify the potential target enzymes of the sole extra and intracellular inhibitor of M. abscessus growth, i.e., compound iBpPPOX, via activity-based protein profiling combined with mass spectrometry. This approach led to the identification of 21 potential protein candidates being mostly involved in M. abscessus lipid metabolism and/or in cell wall biosynthesis. Among them, the Ag85C protein has been confirmed as a vulnerable target of iBpPPOX. This study clearly emphasizes the potential of the OX derivatives to inhibit the extracellular and/or intracellular growth of M. abscessus by targeting various enzymes potentially involved in many physiological processes of this most drug-resistant mycobacterial species.

CLINIC AND COMPLICATIONS OF COVID-19 CORONAVIRUS DISEASE WITH PATHOGENESIS ELEMENTS

The longer the COVID−19 coronavirus pandemic lasts, the more information about its clinical manifestations is accumulated. The incubation period of COVID−19 ranges from 2 to 14 days, rarely up to 3 weeks, but in a significant number of cases an infection is not accompanied with the appearance of clinical symptoms. Currently, the following variants of the clinical course of COVID−19 can be identified as follows: viral load; subclinical; slight; uncomplicated with damage to only the upper respiratory tract; mild pneumonia, severe pneumonia, acute respiratory distress syndrome, etc. The clinical course of COVID−19 depends on the severity, the criteria of which are the intoxication manifestation, the degree of fever and the dominant syndrome. Mild / moderate forms are manifested by frequent increase in body temperature up to 38 ° C, respiratory symptoms, headache, myalgias, palpitations and general malaise. Patients stop distinguishing smells and feel the taste of food. Approximately from the 7th to the 9th days of the disease there are problems with breathing, which indicates the impairment of the lower respiratory tract and the beginning of the second phase of the disease, and its course is regarded as severe. Severe forms of the disease can also be manifested by impaired coordination of movements, slurred speech. In 1 to 4 % of patients there is developed the psychosis in the form of hallucinations. In the elderly, COVID−19 may be accompanied by delirium, lowering blood pressure. The risks of adverse disease are associated with somatic diseases: cardiovascular and nervous systems, respiratory tract, hormonal disorders, etc. Otitis, sinusitis, sepsis, bronchopulmonary infection, thrombosis, myocarditis etc. can be the complications of COVID−19. Computer tomography is an instrumental test that demonstrates the damage of lungs with coronavirus and allows to assess its severity. Key words: coronavirus infection, COVID−19, clinical variants, severity, pneumonia, acute respiratory distress syndrome.

Mortality at the pediatric emergency unit of the Mohammed VI teaching hospital of Marrakech

BackgroundThe death of a child at the emergency ward is one of the most difficult problems that the clinicians of these wards have to deal with. In our country the published data concerning the causes and the factors related to pediatric mortality especially in the pediatric emergency wards is very rare. This study aimed to study the epidemiology of the pediatric mortality in the pediatric emergency department (PED), to determine its rate and identify its most frequent causes.MethodsIt is a retrospective and descriptive study, over five years (1st January 2012 and 31st December 2016) including all children aged from 0 to 15 years old who died at the PED in the Mohamed VI Hospital in Marrakech.ResultsDuring the period of the study a total of 172.691 patients presented to the PED, among which 628 died (pediatric mortality rate: 3.63%). The masculine gender was predominant (n = 383) with a gender ratio of 1.59. Two-thirds of the patients died in the first 24 h (n = 421). The median of time from admission to death was around 12 h. Majority of the deceased children (n = 471, 75%) were from a low socioeconomic status. The most frequent cause of admissions for deceased patients in the PED was respiratory distress (n = 296, 47%) followed by neurological disorders (n = 70, 11%). Neonatal mortality (≤ 1 month of age) was predominant (n = 472, 75.1%), followed by postnatal mortality (1 month to 1 year old) (n = 73, 11.6%). The most frequent causes of pediatric mortality, whatever the age range, were dominated by neonatal pathologies (n = 391, 62.3%), followed by infecious causes bronchopulmonary infections included (n = 49, 7.7%), birth deformities (n = 46, 7.3%) while traumas were merely at 0.9% (n = 6). The most frequent causes of neonatal mortality were neonatal infections (n = 152, 32.2%) and prematurity (n = 115, 24.4%).ConclusionOur data once again underline the crucial importance of prevention. This requires correct follow-up of the pregnancies, an adequate assistance of births, and perfecting healthcare provision to newborns in order to attain proper assistance.

Is bronchoscopic view a reliable method in diagnosis of tracheobronchial aspergillosis in critically ill non-neutropenic patients?

Pulmonary aspergillosis is the main respiratory fungal infection however; its diagnosis is missed or delayed in critically ill non-neutropenic patients. Despite the utility of fiberoptic bronchoscopy for the evaluation of tracheobronchial aspergillosis (TBA) in immunocompromised patients has been extensively studied, however its utility in critically ill non-neutropenic patients is underestimated. To assess the bronchoscopic changes suspected TBA relative to the microbiological and histopathological aspects in critically ill non-neutropenic patients admitted to respiratory intensive care unit (RICU). We prospectively studied 139 critically ill non-neutropenic patients admitted to RICU and had a clinical suspicion of broncho-pulmonary Aspergillus infection. Those patients were subjected to clinical and bronchoscopic assessment for the evaluation of suspected TBA. Microbiological culture of bronchoalveolar lavage (BAL) and histopathological examination of tracheobronchial biopsies were done. Bronchoscopic changes suspected TBA were found in 48.2% of patients (67/139), where Aspergillus infection was confirmed microbiologically in 59.7% (40/67) and histopathologically in 56.7% (38/67). Of these changes, whitish plaques ± ulcers, pseudomembrane and/or sticky secretion with hyperemic mucosa were detected in 68.7%, 26.9% and 16.4% respectively. These changes were mostly seen in the main bronchi (54/67; 80.6%). The sensitivity, specificity, positive, negative predictive values and overall accuracy of these bronchoscopic changes as compared with BAL fluid results were 83.3%, 70.3%, 53.2%, 91.2% and 74.1% respectively. Bronchoscopy could be a reliable procedure for TBA diagnosis in critically ill non-neutropenic patients. Whitish plaques ± ulcers were the prominent bronchoscopic changes with reasonable diagnostic accuracy for prediction of TBA.

Haemophilus influenzae persists in biofilm communities in a smoke-exposed ferret model of COPD.

RationaleNon-typeable Haemophilus influenzae (NTHi) is a common inhabitant of the human nasopharynx and upper airways that can cause opportunistic infections of the airway mucosa including bronchopulmonary infections in patients with chronic obstructive pulmonary disease (COPD). It is clear that opportunistic infections contribute significantly to inflammatory exacerbations of COPD; however, there remains much to be learned regarding specific host and microbial determinants of persistence and/or clearance in this context.MethodsIn this study, we used a recently described ferret model for COPD, in which animals undergo chronic long-term exposure to cigarette smoke, to define host–pathogen interactions during COPD-related NTHi infections.ResultsNTHi bacteria colonised the lungs of smoke-exposed animals to a greater extent than controls, and elicited acute host inflammation and neutrophilic influx and activation, along with a significant increase in airway resistance and a decrease in inspiratory capacity consistent with inflammatory exacerbation; notably, these findings were not observed in air-exposed control animals. NTHi bacteria persisted within multicellular biofilm communities within the airway lumen, as evidenced by immunofluorescent detection of bacterial aggregates encased within a sialylated matrix as is typical of NTHi biofilms and differential bacterial gene expression consistent with the biofilm mode of growth.ConclusionsBased on these results, we conclude that acute infection with NTHi initiates inflammatory exacerbation of COPD disease. The data also support the widely held hypothesis that NTHi bacteria persist within multicellular biofilm communities in the lungs of patients with COPD.

Does PDT have potential in the treatment of COVID 19 patients?

The corona virus pandemic has ignited a proliferation of research aimed at prevention of spread, early diagnosis and treatment. Coincidentally, in recent years the Yorkshire Laser Centre has been engaged in developing the methodology of applying PDT in chronic bronchiectasis. Our methodology is based on Methylene Blue (MB) mediated PDT used topically within the airway. The novelty of the method is the use of a nebulizer to deliver the photosensitizer. We suggest that our protocol and methodology could be modulated for use in respiratory infections of COVID -19.

Continuation of mTOR Inhibition in LAM Patients Listed for Lung Transplant is Safe

Use of mammalian target of rapamycin (mTOR) inhibitors in lymphangioleiomyomatosis (LAM) is now standard of care.1 However, in LAM patients listed for lung transplant (LTX), mTOR inhibitors are often held, as sirolimus has been associated with anastomotic dehiscence2,3. This hold can lead to accelerated respiratory failure. In a survey of LTX programs, 35.4% did not allow patients to remain on mTOR therapy while on the wait list4. We sought to collect a case series of patients who remained on mTOR inhibitors while on the waitlist and describe their outcomes after LTX. Pulmonologists who had managed LAM patients with LTX and continued mTOR inhibitor were contacted. Information was collected from those providers, pertaining to mTOR inhibitor use, airway complications, and transplant outcomes. Eight LAM patients were identified as having been on mTOR inhibitor up until call-in for LTX. Average ages at diagnosis and at LTX were 38.5 years and 48.2 years, respectively. The mTOR inhibitor was started 46.8 months before LTX, with a mean time between listing and LTX of 10.5 months. Seven patients had sporadic LAM, and one had tuberous sclerosis complex-associated LAM. mTOR inhibitor was continued at time of listing in all patients. Three were on sirolimus prior to listing; in two of those patients, sirolimus was switched to everolimus at time of listing. After LTX, mTOR inhibition was resumed in 4 of 8 patients, at a mean of 0.85 years after LTX. One patient had a significant airway complication, a partial right mainstem dehiscence with subsequent stenosis requiring stenting, and recurrent bronchopulmonary infections. She remains alive at 11.3 months after transplant at time of survey. No other patients had wound healing issues. All were alive at time of survey, at a median of 34.9 months after LTX (range, 11.3 to 115.0 months). While controversy abounds regarding the use of mTOR inhibitors during while listed for LTX in LAM patients, this case series suggest that continuation of mTOR inhibitor during waitlist phase before LTX is reasonable and safe. Programs should consider allowance of mTOR inhibition in LAM patients on the LTX waitlist.

Effects of fixed oil of Caryocar coriaceum Wittm. Seeds on the respiratory system of rats in a short-term secondhand-smoke exposure model

Ethnopharmacological relevancePequi fruit are obtained from the pequi tree (Caryocar coriaceum), from which the pulp and nut are used in order to extract an oil that is commonly used in popular medicine as an antiinflammatory agent, particularly for the treatment of colds, bronchitis and bronchopulmonary infections. Making use of the fixed oil of Caryocar coriaceum (FOCC), an attractive alternative for the treatment of diseases caused by exposure to environmental tobacco smoke. Aim of the study:To evaluate whether oral intake FOCC provides beneficial effects in the respiratory system of rats submitted to a short-term secondhand smoke (SHS) exposure model. Materials and methodsThe experiments were performed on Wistar rats divided into 4 groups; in the SHS + O and SHS + T groups, the animals were pretreated orally with 0.5 mL of FOCC (SHS + O) or vehicle (Tween-80 [1%] solution) (SHS + T). Immediately after pretreatment, the animals were submitted to the SHS exposure protocol, for a total period of 14 days. Exposures were performed 6 times per day, with a duration of 40 min per exposure (5 cigarettes per exposure), followed by a 1-h interval between subsequent exposures. In the AA + O and AA + T groups, animals were submitted to daily oral pretreatment with 0.5 mL of FOCC (AA + O) or vehicle (AA + T). These animals were then subjected to the aforementioned exposure protocol, but using ambient air. After the exposure period, we investigated the effects of FOCC in respiratory mechanics in vivo (Newtonian resistance -RN, tissue elastance -H, tissue resistance -G, static compliance -CST, inspiratory capacity -IC, PV loop area) histopathology and lung parenchymal morphometry in vitro (polymorphonuclear cells –PMN, mean alveolar diameter -Lm, bronchoconstriction index -BCI), temporal evolution of subjects’ masses, and percent composition of the FOCC. ResultsRegarding the body mass of the animals, the results demonstrated an average body mass gain of 10.5 g for the animals in the AA + T group, and 15.5 g for those in the AA + O group. On the other hand, the body mass of animals in the SHS + T and SHS + O suffered an average loss of 14.4 and 4.75 g, respectively. Regarding respiratory system analyzes, our results demonstrated significant changes in all respiratory mechanics variables and lung parenchyma morphometry analyzed for the SHS + T group when compared to the AA + T group (p < 0,05), confirming the establishment of pulmonary injury induced by SHS exposure. We also observed that rats pretreated orally with FOCC (SHS + O) showed improvement in all variables when compared to the SHS + T group (p < 0,05), thus demonstrating the effectiveness of FOCC in preventing lung damage induced by short-term SHS exposure. ConclusionIn conclusion, our results demonstrate that FOCC was able to prevent lung injury in rats submitted to short-term SHS exposure.

Lophomonas blattarum: A new flagellate causing respiratory tract infections.

Lophomonas blattarum is a flagellate protozoan parasite which was originally described as a commensal in the gut of cockroaches. From the 1990s, reports started coming out of peoples Republic of China about its possible role in bronchopulmonary infections, and this was followed by reports from some other parts of the world as well. There had been some skepticism regarding the misidentification of bronchial ciliated epithelial cells as L. blattarum, but recent use of molecular diagnosis has come as an aid in clearing the controversy. This review focuses on the various aspects of the parasite including its biology, epidemiology, clinical manifestations, laboratory diagnosis, and the treatment aspects. Molecular diagnosis has recently been employed and more reports concerning its validation is needed. More basic research concerning the genomic and proteomic analysis is necessary to develop reliable molecular and serological tests for this parasite in future.

Pharmacochemical Aspects of the Evolution from Erythromycin to Neomacrolides, Ketolides and Neoketolides

Antibiotic macrolides are experiencing renewed interest in anti-infective therapy since the advent of ketolides. This therapeutic class was introduced in order to broaden the narrow antibacterial spectrum of macrolides and to cope with the emergence of germs resistant to Erythromycin A and its hemisynthetic derivatives or neomacrolides (Clarithromycin, Roxithromycin, Azithromycin, Dirithromycin). From a pharmacochemical point of view, ketolides were first of all obtained by operating chemical modulations on Erythromycin A to obtain the neomacrolides, then, by replacing the neutral sugar (L-cladinose) in C3 by a ketone function coupled with the creation of an oxazolidinone like heterocycle in C11 and C12 in place of the hydroxyls present in these positions (Telithromycin, Cethromycin, Solithromycin). These modulations have enabled the improvement of the chemical stability of ketolides in gastric acid medium and increase their affinity for the ribosomal target, hence the broadening of their spectrum of action towards Gram positive germs including strains resistant to other macrolides and to neomacrolides. Therefore, the objective of this systematic review is to report the various pharmacochemical aspects undertaken since 1952 in the macrolide series based on the structure of Erythromycin A. These aspects will focus on the pharmacomodulations that have led, year after year, to the optimization of stability, the improvement of the pharmacodynamic and pharmacokinetic profile and that have allowed the development of neomacrolides, ketolides and neoketolides, which are today essential in the management of severe bronchopulmonary infections.

“Video Assisted Thoracoscopic Surgery (VATS) for all Stages of Empyema Thoracis: a Single Centre Experience”

Video assisted thoracoscopic surgery (VATS) is a surgical treatment option for empyema thoracis (ET). However, very few studies have been reported from India. The present study aims to evaluate the role, implementation and outcomes of VATS for all stages of ET. A prospective evaluation of 33 patients with ET managed by VATS decortication from January 2016 to December 2017 was performed. All were followed up for 6 months to evaluate surgical outcomes, conversion rate, morbidities and relapse.Out of 33, 5 patients had stage I, 18 had stage II and 10 had stage III empyema. Most common symptoms were dyspnea [75.75%] and fever [63.63%]. Commonest etiology was bronchopulmonary infection (51.51%) and tuberculosis (33.33%). Conversion rate was 3.03%. Mean operating time was 102, 178.8 and 323 min for stage I, II, III respectively. Mean hospital stay for stage I, II,III was 4, 5.11 and 9.3 days respectively. Intraoperative bleeding was high in stage III (625 ml) compared to stage II (327.7 ml). Mean chest tube duration for stage I, II and III was 13.4, 10.2 and 14.8 days respectively. VATS decortication is safe, feasible and effective treatment for all ET stages, when preformed in properly selected patients at appropriate time by experienced surgeons. It improves outcomes in stage I ET by reducing recurrence in cases with failure of conservative management. When timed appropriately, it has acceptable morbidity and postoperative recovery rates without significant conversion rates, even in stage III ET.

EFFECTIVENESS OF AN EXPIRATORY FLOW ACCELERATION DEVICE IN DYSPHAGIC PATIENTS WITH PARKINSON DISEASE

SESSION TITLE: Wednesday Electronic Posters 5 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Parkinson's disease causes dysfunction both to swallowing in its various phases as well as to the mechanism of cough. Oropharyngeal dysphagia is present at all stages of the disease, and is the main cause of pneumonia due to silent aspiration of food and saliva. Hence, it may increase the risk of death, pneumonia being often the final cause of death . Different strategies exist to reduce the risk of inhalation, and consequently the risk and number of lung infections. In this preliminary study, we aimed to evaluate whether adding to the standard therapy a technique designed to accelerate the expiratory flow could reduce the number of inflammatory events. Our aim was to investigate the efficacy of the Expiratory Flow Acceleration (EFA) technique, applied using the device Free Aspire®, to reduce the incidence of bronchopulmonary infections . Moreover, changes in respiratory function parameters, cough and encumbrance and quality of life ( QoL) scores METHODS: Twenty patients with Parkinson' s disease were enrolled (13 males and 7 females. Inclusion criteria were:-Stage III and IV of the H&Y classification (Hoehn & Yahr scale)-Score 3-4 on the DOSS scale (Dysphagia Outcome and Severity Scale)-Score ≥ 5 on the Pooling Score-Score ≥ 4 on the PAS scale (Penetration Aspiration Scale) Treatment-10 patients treated with standard therapy + EFA with Free Aspire®-10 patients treated with standard therapy (control group) Re-evaluation at 30 - 60 - 180 days after the start of treatment Primary outcome : the incidence of bronchopulmonary infections in patients with Parkinson's disease affected by swallowing deficits Secondary outcomes : - Respiratory function tests (FVC, FEV1), Cough capacity test (PCEF) Questionnaires on QoL (Euro-QOL, PDQ-39),VAS (Visual Analogue Scale) for cough and bronchial encumbrance. RESULTS: Among the primary outcomes, no significant difference was found between the two groups as regards the number of respiratory infections, number of accesses to the Emergency Department, or number of admissions. Secondary outcomes ( spirometric parameters[FEV1 and CVF),cough effectiveness(PCEF)and questionnaire of QoL showed a significant improvement in the EFA group compared to the control group . CONCLUSIONS: The treatment with the EFA device seems to lead to an improvement in the functional indices as well as in the quality of life of Parkinson's patients with dysphagia. Nevertheless, definitive conclusions cannot be drawn due to the small sample size. The results of this pilot study seem to support the effectiveness of the treatment with EFA technology. However, further studies are needed in a larger, and hence more representative, sample of patients in order to be able to definitively confirm the usefulness of this technique for this type of patient. CLINICAL IMPLICATIONS: Adding EFA technology to standard therapy is useful for Parkins's disease patients with swallowing disorders DISCLOSURES: No relevant relationships by NICOLINI ANTONELLO, source=Web Response No relevant relationships by Bruna Grecchi, source=Web Response

The Emergence of Rare Clinical Aspergillus Species in Qatar: Molecular Characterization and Antifungal Susceptibility Profiles

Aspergillus are ubiquitous mold species that infect immunocompetent and immunocompromised patients. The symptoms are diverse and range from allergic reactions, bronchopulmonary infection, and bronchitis, to invasive aspergillosis. The aim of this study was to characterize 70 Aspergillus isolates recovered from clinical specimens of patients with various clinical conditions presented at Hamad general hospital in Doha, Qatar, by using molecular methods and to determine their in vitro antifungal susceptibility patterns using the Clinical and Laboratory Standards Institute (CLSI) M38-A2 reference method. Fourteen Aspergillus species were identified by sequencing β-tubulin and calmodulin genes, including 10 rare and cryptic species not commonly recovered from human clinical specimens. Aspergillus welwitschiae is reported in this study for the first time in patients with fungal rhinosinusitis (n = 6) and one patient with a lower respiratory infection. Moreover, Aspergillus pseudonomius is reported in a patient with fungal rhinosinusitis which is considered as the first report ever from clinical specimens. In addition, Aspergillus sublatus is reported for the first time in a patient with cystic fibrosis. In general, our Aspergillus strains exhibited low MIC values for most of the antifungal drugs tested. One strain of Aspergillus fumigatus showed high MECs for echinocandins and low MICs for the rest of the drugs tested. Another strain of A. fumigatus exhibited high MIC for itraconazole and categorized as non-wild type. These findings require further analysis of their molecular basis of resistance. In conclusion, reliable identification of Aspergillus species is achieved by using molecular sequencing, especially for the emerging rare and cryptic species. They are mostly indistinguishable by conventional methods and might exhibit variable antifungal susceptibility profiles. Moreover, investigation of the antifungal susceptibility patterns is necessary for improved antifungal therapy against aspergillosis.

B.02 Long-term neurodevelopmental outcomes in preterm twins

Background: Preterm infants are at risk for adverse neurodevelopmental outcomes, however studies examining preterm twins are limited. The aim of this study was to examine whether preterm monozygotic (MZ) and dizygotic (DZ) twins have similar morbidities and long-term neurodevelopmental outcomes. Methods: From a cohort of 225 preterm neonates studied with MRI, 24 MZ and 52 DZ twins were included. Outcomes at 1.5-years, 3-years and 4.5-years were assessed with the Bayley-III, Movement Assessment Battery for Children and Wechsler Preschool and Primary Scale of Intelligence. Results: Twin pairs had substantial concordance for retinopathy of prematurity but only moderate-fair concordance for bronchopulmonary dysplasia, infection and brain injury. Differences in cognitive and language scores were stable over time, while motor differences increased. Discordant twins had significantly lower gestational age [Mean1(SD)=26.7(1.38); Mean2(SD)=29.1(2.1); P&amp;lt;0.001] and birth weight [Mean1(SD)=892.2(291.2); Mean2(SD)=1208.0(289.4); P=0.001] and a higher incidence of bronchopulmonary dysplasia and retinopathy of prematurity. In discordant twins, cognitive and language score differences decreased over time while motor differences increased. Conclusions: Preterm twin pairs have similar neurodevelopmental outcomes through early childhood despite poor concordance for perinatal illness. Discordant twins were born earlier and had more morbidities. Increasing concordance in cognitive and language outcomes over time may reflect the positive impact of early intervention programs.