Lipidomic profiling of amniotic fluid reveals aberrant fetal lung development and fetal growth disrupted by lipid disorders during gestational asthma.

This study aimed to investigate how maternal asthma during pregnancy disrupts fetal lung development by altering lipid metabolism in the amniotic fluid, which is crucial for fetal development. A pregnancy-induced asthma model was established in female rats using house dust mite (HDM) as a common allergen. The fetuses were divided into four groups based on whether the mother and fetus were exposed to the allergen: PBS+PBS, PBS+HDM, HDM+PBS, and HDM+HDM. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to analyze changes in the lipid profile of the amniotic fluid and bronchoalveolar lavage fluid (BALF). Principal component analysis (PCA) and ChemRICH methods were used to explore the potential relationship between lipid metabolism abnormalities and impaired fetal lung development. The results indicate that maternal asthma exacerbates asthma-related inflammatory markers in fetuses, leading to pathological changes in the lungs and elevated levels of cytokines IL-5, IL-13, and IgE. Additionally, 18 differential lipids, primarily oxygenated lipids, were identified in the amniotic fluid after modeling, suggesting an enhanced oxidative stress environment for the fetus. This environment causes metabolic disturbances in various lipid groups in fetal lungs, with the HDM+HDM group showing significant abnormalities in lipids critical for lung development, including phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and fatty acids (FA). In conclusion, gestational asthma can reshape the lipid profile in the amniotic fluid and BALF, significantly disrupting fetal growth and lung development. Restoring normal lipid metabolism in the amniotic fluid and fetal lungs may offer a potential therapeutic approach to managing aberrant fetal lung development in asthmatic mothers.

Incidence of Pneumonia following Bronchoscopy and Bronchoalveolar Lavage in Burn Patients.

The standard modality for diagnosis of smoke inhalational injury in burn patients is bronchoscopy with or without bronchoalveolar lavage. However, the risks associated with these procedures are poorly described in established literature. We sought to investigate the association between diagnostic bronchoalveolar lavage at admission and the development of pneumonia in burn patients. This retrospective analysis of intubated burn patients studied those who underwent bronchoscopy on admission, comparing patients who received bronchoalveolar lavage to those who did not. Demographics and baseline characteristics were analyzed using chi-squared or Student's t-test. Unadjusted and multivariable logistic regression studies assessed the effect of admission bronchoalveolar lavage on development of pneumonia. Out of the 196 patients who underwent bronchoscopy, 98 met our criteria for analysis. The bronchoalveolar lavage group was more likely to be male and have a higher grade of abbreviated injury score. Patients who received bronchoalveolar lavage were more likely to develop pneumonia during the admission in both unadjusted and multivariable logistic regression models. These patients also had a longer hospital length of stay, greater number of ventilator days, and were more likely to undergo second bronchoscopy. These findings associate admission bronchoalveolar lavage with increased risk of pneumonia during the index hospitalization, suggesting a judicious use of bronchoalveolar lavage during admission bronchoscopy in burn patients.

Non-tuberculous mycobacteria enhance the tryptophan-kynurenine pathway to induce immunosuppression and facilitate pulmonary colonization.

The increasing prevalence of non-tuberculous mycobacterium (NTM) infections alongside tuberculosis (TB) underscores a pressing public health challenge. Yet, the mechanisms governing their infection within the lung remain poorly understood. Here, we integrate metagenomic sequencing, metabolomic sequencing, machine learning classifiers, SparCC, and MetOrigin methods to profile bronchoalveolar lavage fluid (BALF) samples from NTM/TB patients. Our aim is to unravel the intricate interplay between lung microbial communities and NTM/Mycobacterium tuberculosis infections. Our investigation reveals a discernible reduction in the compositional diversity of the lung microbiota and a diminished degree of mutual interaction concomitant with NTM/TB infections. Notably, NTM patients exhibit a distinct microbial community characterized by marked specialization and notable enrichment of Pseudomonas aeruginosa and Staphylococcus aureus, driving pronounced niche specialization for NTM infection. Simultaneously, these microbial shifts significantly disrupt tryptophan metabolism in NTM infection, leading to an elevation of kynurenine. Mycobacterium intracellulare, Mycobacterium paraintracellulare, Mycobacterium abscessus, and Pseudomonas aeruginosa have been implicated in the metabolic pathways associated with the conversion of indole to tryptophan via tryptophan synthase within NTM patients. Additionally, indoleamine-2,3-dioxygenase converts tryptophan into kynurenine, fostering an immunosuppressive milieu during NTM infection. This strategic modulation supports microbial persistence, enabling evasion from immune surveillance and perpetuating a protracted state of NTM infection. The elucidation of these nuanced microbial and metabolic dynamics provides a profound understanding of the intricate processes underlying NTM and TB infections, offering potential avenues for therapeutic intervention and management.

Occupational Diffuse Alveolar Hemorrhage Due to Metal Fume and Nitric Acid Exposure: A Case Report.

A 52-year-old male welder, who had been exposed to metal fumes and nitric acid without adequate protective measures, presented with symptoms of cough, dyspnea, and fever. He was admitted to our hospital, where bronchoscopy revealed hemorrhagic bronchoalveolar lavage fluid. He was diagnosed with diffuse alveolar hemorrhage (DAH) due to occupational inhalation of metal fumes and nitric acid. Treatment with corticosteroids led to a rapid recovery without pulmonary sequelae. The case highlights the potential for metal fumes and/or nitric acid to induce DAH, the effectiveness of corticosteroids in treating the condition, and the critical importance of occupational protective measures.

A case of pulmonary mucosa-associated lymphoid tissue lymphoma diagnosed by detecting t(11;18)(q21;q21) in bronchial lavage fluid.

A 76-year-old woman was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma by upper gastrointestinal endoscopy. She underwent further investigation for concomitant bilateral pleural effusions and right pulmonary consolidation. MALT lymphoma with the t(11; 18)(q21; q21) translocation and API2-MALT1 were detected in pleural fluid. Lymphoma was not histopathologically diagnosed by lung biopsies, but the same translocation was identified in bronchial lavage. MALT lymphoma is often difficult to diagnose by bronchoscopy because of only mild dysplasia. However, present report on using chromosomal translocation analysis from bronchial lavage indicates that such testing may serve as a useful diagnostic adjunct in MALT lymphoma with lung involvement.

Exposure to respirable silica contributes to lower airway inflammation in asthmatic horses.

BACKGROUND: Respirable mineral particles can induce lower airway inflammation, but the role they play in asthma of horses is unknown. OBJECTIVES: Respirable mineral particles, particularly respirable silica, are an overlooked determinant of chronic lung inflammation (asthma) in horses. ANIMALS: Twenty-three horses from an equine hospital population: 11 moderately affected (MEA), 7 severely asthmatic (SEA), and 5 control horses free from respiratory clinical signs. METHODS: Prospective observational study. The quantity and quality of mineral particles found in bronchoalveolar lavage fluid (BALF) were characterized, with particular attention to silica content. Polarized light microscopy performed on cytospin slides identified intracellular birefringent particles as silica. Spectrometry-based analysis performed on whole BALF determined total mineral and silica percentage and concentration. Group-related differences in BALF mineral and silica load were investigated as well as associations with BALF cytology. RESULTS: Intracellular birefringent particles were increased in SEA vs MEA (median [interquartile range, IQR]), 12 [7] vs 4 [5] particles/30 high power fields [hpf], respectively; P = .01) and vs controls (4 [2] particles/30 hpf; P = .02). Total mineral concentration in BALF was similar between the groups studied, whereas silica concentration and percentage were increased in SEA vs MEA (1758 [887] particles/mL and 20 [10]% vs 867 [662] particles/mL and 8 [6]%; P = .009 and P = .001) and control group (355 [330] particles/mL and 6 [3]%; P = .0003 and P = .002). Silica load in BALF was associated with BALF neutrophilia in MEA and SEA. CONCLUSIONS AND CLINICAL IMPORTANCE: Respirable silica is associated with neutrophilic lower airway inflammation in horses and might contribute to asthma development.

Efficacy of added splint therapy after arthrocentesis vs arthrocentesis alone in the management of temporomandibular joint disorders: a systematic review and meta-analysis.

OBJECTIVE: Occlusal splints are commonly used in the management of temporomandibular joint (TMJ) disorders (TMD). However, it is unclear if it should be used after a second-line therapy like arthrocentesis. We systematically reviewed the evidence on the efficacy of post-arthrocentesis splint therapy in the management of TMD. METHODS: PubMed, Embase, Scopus, Web of Science, CENTRAL, and Google Scholar were searched for studies published until 5th August 2024. The outcomes assessed were pain and maximal mouth opening (MMO). RESULTS: Eight studies were included. Five studies reported data for the meta-analysis. The pooled analysis found that there was no statistically significant difference in pain scores in the arthrocentesis + splint group vs arthrocentesis group at 1 month (MD: -0.01 95% CI: -0.46, 0.44), 3 months (MD: -0.02 95% CI: -0.67, 0.63) and 6 months (MD: 0.06 95% CI: -0.25, 0.37). The pooled analysis also showed that splint therapy after arthrocentesis may not significantly improve MMO as compared to no splint therapy at 1 month (MD: 0.08 95% CI: -2.11, 2.27), 3 months (MD: 0.76 95% CI: -0.84, 2.35) and 6 months (MD: 0.56 95% CI: -0.65, 1.78). Descriptive analysis of three studies showed that two supported the use of splints while one found no added improvement in outcomes. CONCLUSIONS: Limited evidence from low-quality studies shows that the use of splint therapy after arthrocentesis may not improve pain and MMO in patients with TMD. High-quality randomized controlled trials are needed to improve evidence.

Blood culture-negative Haemophilus endocarditis with large vegetation and the role of bronchoalveolar lavage: a case report.

Background: Blood culture-negative endocarditis (BCNE) is a significant condition associated with cardiac vegetation. It often occurs alongside sepsis, auto-immune diseases, or malignancies, posing a risk of vegetation and embolization. Notable pathogens include Haemophilus species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species. Case summary: A 60-year-old white male Belgian patient presented with worsening dyspnoea. His recent medical history included chronic infections over the past 6 months. Transthoracic echocardiography revealed severe aortic stenosis with an 18 × 12 mm vegetation. Despite normal inflammatory markers and negative blood tests, 18F-fluorodeoxyglucose positron emission tomography with computed tomography excluded malignancy but identified multiple bilateral septic lung emboli. Sputum cultures and tuberculosis polymerase chain reaction (PCR) were negative. Facing the high risk of cardiac embolization and the need for aortic valve replacement, surgery was scheduled with an intraoperative bronchoalveolar lavage (BAL) to investigate the lung lesions. Intraoperative findings confirmed valvular lesions, and a biological aortic valve was successfully implanted. The post-operative course was uneventful. Aortic valve cultures and eubacterial PCR results were negative, but BAL cultures were positive for Haemophilus influenzae, indicating a chronic infection. The patient showed favourable progress at 6 months post-surgery with ongoing antibiotherapy. Discussion: This case illustrates a rare BCNE associated with large vegetation and symptomatic H. influenzae chronic respiratory tract colonization (CRTC). For BCNE cases with negative sputum cultures and suspected bacterial CRTC, we recommend performing BAL cultures for accurate diagnosis.

"To BAL or not to BAL, that is the question": Variations in smoke inhalation injury guidelines from burn units and centres in England, Scotland and Wales.

AIM: To evaluate variations in diagnostic criteria and management recommendations for smoke inhalation injury (SII) amongst the burn networks of England, Scotland, and Wales. METHODS: A descriptive cross-sectional study examining SII guidelines provided by adult burn units and centres in England, Scotland and Wales. RESULTS: All 16 adult burn units and centres responded. Fourteen (87.5 %) had guidelines. Due to sharing of guidelines, ten unique guidelines were assessed. Diagnostic criteria showed variability with no universal criterion shared amongst guidelines. Bronchoscopy was recommended by 90 % of guidelines, but the timing varied. The use of bronchoscopic scoring systems was recommended by four guidelines. Bronchoalveolar lavage (BAL) was recommended by four, with considerable variation in frequency and choice of lavage fluid. All guidelines advised at least one nebulised agent: heparin (n = 8); N-acetyl cysteine (NAC) (n = 8); or salbutamol (n = 8). All guidelines included advice on carbon monoxide poisoning; however, carboxyhaemoglobin (COHb) cut-off levels for treatment varied (5 % [n-4], 10 % [n = 3], 15 % [n = 1]). All recommended high-flow oxygen. Seven (70 %) guidelines offered guidance on cyanide poisoning. Reduced/altered consciousness was the only consistent diagnostic criterion. Five (50 %) guidelines provided intubation guidance, emphasising the role of a 'senior clinician' as the intubator. Ventilatory guidance appeared in eight guidelines, focusing on lung protective ventilation (n = 8); oxygenation goals (n = 3); and permissive hypercapnia (n = 3). Within lung-protective ventilation, advice on tidal volume (6, or 6-8 ml/kg) and plateau pressures (>30 cmH2O) were presented most commonly (n = 7). CONCLUSION: This study has outlined the substantial variations in guidance for the management of SII. The results underscore the need for a national guideline outlining a standardised approach to the diagnosis and management of SII, within the limitations of the current evidence.

The clinical application of metagenomic next-generation sequencing in immunocompromised patients with severe respiratory infections in the ICU.

BACKGROUND: Early targeted antibiotic therapy is crucial for improving the prognosis of immunocompromised patients with severe respiratory infections (SRIs) in the intensive care unit (ICU). Metagenomic next-generation sequencing (mNGS) has shown significant value in pathogen detection, but research on lower respiratory tract microorganisms remains limited. METHODS: This study enrolled 234 patients with SRIs in the ICU, and individuals were categorized into immunocompromised and immunocompetent groups. We compared the diagnostic performance of mNGS using bronchoalveolar lavage fluid (BALF) with conventional microbiological tests (CMTs) and analyzed the value of mNGS in immunocompromised patients with SRIs in the ICU. RESULTS: Among all patients, the pathogenic microorganism detection rate of mNGS was higher than that of CMTs (94.02% vs 66.67%, P < 0.05), both in the immunocompromised group (95.0% vs 58.75%, P < 0.05) and the immunocompetent group (93.51% vs 71.43%, P < 0.05). mNGS detected more pathogens than CMTs did (167 vs 51), identifying 116 organisms that were missed by CMTs. The proportion of antibiotic regimen adjustments based on mNGS results was significantly higher compared to CMTs in both the immunocompromised (70.00% vs 17.50%, P < 0.05) and immunocompetent groups (48.70% vs 15.58%, P < 0.05). In the immunocompromised group, patients who had their antibiotic treatment adjusted on mNGS results had improved prognosis, with significantly lower ICU mortality (8.93% vs 50%, P < 0.05) and 28-day mortality rates (30.36% vs 68.75%, P < 0.05) than CMTs. In the immunocompetent group, no statistically significant differences were observed in ICU mortality or 28-day mortality (20.00% vs 33.33%, P > 0.05; 42.67% vs 45.83%, P > 0.05). CONCLUSION: mNGS shows significant value in detecting pathogens in immunocompromised patients with SRIs in ICU. For immunocompromised patients who respond poorly to empirical treatment, mNGS can provide an etiological basis, helping adjust antibiotic regimens more precisely and thereby improving patient prognosis.

Diagnostic Value of Metagenomic next-generation sequencing and X-pert in Bronchoalveolar lavage fluid for pneumonia in HIV-infected and HIV-uninfected patients.

Background: The pathogens causing unexplained pneumonia in both HIV-infected or HIV-unfected patients are likely to be complex. This retrospective study aimed to characterize the etiology of pneumonia in HIV-infected and HIV-uninfected patients using bronchoalveolar lavage fluid (BALF) analysis with metagenomic next-generation sequencing (mNGS) and X-pert MTB/RIF. Methods: Between January 2022 and May2024, 141 HIV-infected and 104 HIV-uninfected patients admitted to Nanjing Second Hospital with pneumonia were included. BALF samples were collected and analyzed using mNGS to detect bacteria, fungi, viruses, tuberculosis (TB) and non-tuberculous mycobacteria (NTM), and X-pert for TB detection. Clinical data including CD4 T-cell counts, comorbidities, and ART status were collected and analyzed. Results: HIV-uninfected patients were found to be older and exhibited a higher prevalence of comorbidities compared to HIV-infected patients. Despite higher median CD4 T-cell counts in HIV-uninfected individuals (412 cells/µL vs. 31 cells/µL in HIV-infected), TB detection rates using X-pert and mNGS were lower than anticipated, particularly in HIV-infected patients. Mixed-pathogen infections were significantly more prevalent in HIV-infected patients, especially those with lower CD4 T-cell counts. ART use showed variable impacts on pathogen diversity, with longer treatment durations associated with reduced infection complexity but persistent immunodeficiency in some cases.In patients with pneumonia, whether HIV-infected or HIV-uninfected, pathogens often exhibit complexity, underscoring the critical role of timely mNGS and X-pert analysis of BALF for early pathogen detection.

Tranexamic Acid Neurotoxicity After Nebulization and BAL.

Tranexamic acid is a commonly used hemostatic agent with broad clinical uses across multiple specialties. Systemic toxicity is due to gamma-aminobutyric acid type A and glycine receptor competitive antagonism and has been reported by multiple routes, but toxicity after pulmonary administration via nebulization and BAL has not yet been described. A 44-year-old man with a history of congenital pulmonary arteriovenous malformations underwent routine bronchoscopy for hemoptysis. He received preprocedure nebulized tranexamic acid 500 mg three times daily for 48 h. An additional 1,000 mg was given via BAL for intraprocedural hemostasis. One hour after the procedure, he developed altered mental status, myoclonus, and hyperthermia, which was ultimately controlled with propofol and vecuronium. As the use of pulmonary tranexamic acid increases, toxicity from this agent should be considered. Dose reductions and alternate treatment modalities should be considered in patients with advanced age, arteriovenous malformations, and renal insufficiency.

Allergic rhinitis management: a survey on Italian primary care pediatricians.

Summary: Background. Allergic rhinitis (AR) is a widespread condition. The Italian Society of Pediatric Allergology and Immunology (SIAIP) promoted an initiative to update the knowledge on AR in children and adolescents. The present survey directly addressed primary care pediatricians, thus reflecting the real-world management of AR in children and adolescents. The aim was to investigate common practice in managing AR children. Methods. A panel of experts drafted a series of questions concerning the practical management of children with AR in clinical practice. The questionnaire was administered to a large sample of primary care pediatricians (864). Results. 864 primary care pediatricians participated to the survey. Each pediatrician on average follows 94 children with AR; globally 81,231 children. More than 70% of participants follow ARIA guidelines. Accordingly, 42% of children have mild AR and 58% moderate/severe. Asthma, conjunctivitis and adenoid hypertrophy are the most common comorbidity. Most pediatricians autonomously follow their patients. The intensity of treatment (use of medication) is directly proportional to the symptom severity.  Intranasal corticosteroids are the most common medication used followed by oral antihistamines and nasal lavages (with hypertonic or isotonic solution). Up to 20% of participants prescribe the fixed association topical corticosteroids plus antihistamine. Conclusions. The present survey demonstrated that Italian primary care pediatricians accomplish ARIA guidelines and adapt treatment on the basis of the intensity of symptoms. Corticosteroids and antihistamines are the most common prescribed medications. Nasal lavages are also popular.

Next generation sequencing identifies an increased diversity of microbes in post lavage specimens in infected TKA using a biofilm disrupting irrigant.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of joint arthroplasty. In chronic PJI, a biofilm envelops the surface of implants, which contains microbiota within an extra-microbial polymeric matrix (EMPM). Microbial identification is paramount for effective treatment. In this study, we use a multi-modal, EMPM disrupting, neoadjuvant irrigant and compare the microbiota detected pre-lavage to post-lavage by two techniques: culture and Next Generation Sequencing (NGS). We suspect more organisms to be identified after applying an EMPM disrupting irrigant. METHODS: A multicenter, prospective study was conducted on 38 patients with known Total Knee Arthroplasty PJI. At initial arthrotomy, synovial fluid was obtained and analyzed for quantitative cultures and microbial NGS. Joint was then irrigated with Bactisure Lavage followed by Normal Saline. Post-lavage samples were similarly obtained and analyzed. RESULTS: In pre-lavage samples for cultures, 55.3% of samples were positive, identifying 11 unique organisms. In post-lavage samples for cultures, 13.2% of samples were positive, identifying 5 unique organisms. In pre-lavage samples for NGS, 79% were DNA signal positive, identifying 126 unique organisms. In post-lavage samples for NGS, 74% of samples were DNA signal positive, identifying 177 unique organisms. Moreover, 135/177 of these organisms were not identified pre-lavage. CONCLUSION: In this pre-to-post irrigant study, culture showed a decrease in the number of identifiable organisms post-lavage. In contrast NGS revealed an increase in the number of identifiable organisms post-lavage. Furthermore, NGS identified 135 additional organisms, not detected pre-lavage. This suggests an increased diversity of microbes may exist within EMPM, which are not cultivable.

Microplastics, as a risk factor in the development of interstitial lung disease- a preliminary study.

Microplastic (MPs) pollution is a global concern that affects all living organisms, yet research on MP-related disorders in humans, including incidence and symptoms, remains limited. In this study, the presence, composition, and characterization of MPs in bronchoalveolar lavage (BAL), which reflects lung tissue, and blood were examined. Fiberoptic bronchoscopy was performed to collect BAL samples from patients suspected of having interstitial lung disease (ILD) as well as from a control group. MPs were identified and measured using µ-Raman techniques. In BAL samples, the most common MPs color observed was grey/white, with sizes ranging from 4.19 to 792.00 µm. The particle shapes and polymer types identified included polyamide (PA), polyester (PET), polyvinyl chloride (PVC), and polyurethanes (PU). For blood samples, MPs were predominantly grey/white and blue, with sizes ranging from 13.14 to 20. 29 µm. The identified polymers in blood samples included polyamide (PA) and polyethylene (PE). MPs were detected in 10 out of 18 patients (55%) suspected of having ILD, with most of these patients presenting with the fibrotic type of the disease. In the control group, two patients whose BAL samples were positive for MPs were found to have chronic lung disease. This study is the first to explore the relationship between interstitial lung disease (ILD) and microplastics (MPs), revealing a tendency for the presence of MPs in the bronchoalveolar lavage (BAL) of ILD patients, particularly those with a fibrotic phenotype. Further research is needed to determine the cumulative effects of MPs on human health, especially concerning the respiratory system, which is highly exposed to environmental pollutants.

Transmission electron microscopy of transbronchial lung cryobiopsy samples in a cohort of fibrotic interstitial lung disease patients - feasibility and implications of endothelial alterations.

We evaluated the utility of transmission electron microscopy (TEM) in transbronchial lung cryobiopsy (TBLC) samples from 16 consecutive patients undergoing routine evaluation of fibrotic interstitial lung disease (ILD). Next to routine pathology examination, 1 to 2 TBLC samples were prepared for TEM analysis and evaluated using a Zeiss LEO EM 910. Subpleural cryobiopsies and unfrozen excision biopsies from fresh lobectomy tissue of non-ILD lung cancer patients served as controls. TEM provided high-quality images with only minor cryoartifacts as compared to controls. Furthermore, in several ILD patients we found marked microvascular endothelial abnormalities like luminal pseudopodia-like protrusions and inner surface defects. These were extensively present in four (25%), moderately present in seven (43.8%), and largely absent in five (31.3%) patients. A higher degree of TEM endothelial abnormalities was associated with younger age, non-specific interstitial pneumonia pattern, higher broncho-alveolar lavage lymphocyte count, positive autoantibodies, and lower spirometry, diffusion capacity and oxygenation biomarkers. We conclude that TEM evaluation of TBLC samples from ILD patients is feasible, while the observed microvascular alterations warrant further evaluation.

Microbiome and metabolome patterns after lung transplantation reflect underlying disease and chronic lung allograft dysfunction.

BACKGROUND: Progression of chronic lung disease may lead to the requirement for lung transplant (LTx). Despite improvements in short-term survival after LTx, chronic lung allograft dysfunction (CLAD) remains a critical challenge for long-term survival. This study investigates the molecular and microbial relationships between underlying lung disease and the development of CLAD in bronchoalveolar lavage fluid (BALF) from subjects post-LTx, which is crucial for tailoring treatment strategies specific to allograft dysfunctions. METHODS: Paired 16S rRNA gene amplicon sequencing and untargeted LC-MS/MS metabolomics were performed on 856 BALF samples collected over 10 years from LTx recipients (n = 195) with alpha-1-antitrypsin disease (AATD, n = 23), cystic fibrosis (CF, n = 47), chronic obstructive pulmonary disease (COPD, n = 78), or pulmonary fibrosis (PF, n = 47). Data were analyzed using random forest (RF) machine learning and multivariate statistics for associations with underlying disease and CLAD development. RESULTS: The BALF microbiome and metabolome after LTx differed significantly according to the underlying disease state (PERMANOVA, p = 0.001), with CF and AATD demonstrating distinct microbiome and metabolome profiles, respectively. Uniqueness in CF was mainly driven by Pseudomonas abundance and its metabolites, whereas AATD had elevated levels of phenylalanine and a lack of shared metabolites with the other underlying diseases. BALF microbiome and metabolome composition were also distinct between those who did or did not develop CLAD during the sample collection period (PERMANOVA, p = 0.001). An increase in the average abundance of Veillonella (AATD, COPD) and Streptococcus (CF, PF) was associated with CLAD development, and decreases in the abundance of phenylalanine-derivative alkaloids (CF, COPD) and glycerophosphorylcholines (CF, COPD, PF) were signatures of the CLAD metabolome. Although the relative abundance of Pseudomonas was not associated with CLAD, the abundance of its virulence metabolites, including siderophores, quorum-sensing quinolones, and phenazines, were elevated in those with CF who developed CLAD. There was a positive correlation between the abundance of these molecules and the abundance of Pseudomonas in the microbiome, but there was no correlation between their abundance and the time in which BALF samples were collected post-LTx. CONCLUSIONS: The BALF microbiome and metabolome after LTx are particularly distinct in those with underlying CF and AATD. These data reflect those who developed CLAD, with increased virulence metabolite production from Pseudomonas, an aspect of CF CLAD cases. These findings shed light on disease-specific microbial and metabolic signatures in LTx recipients, offering valuable insights into the underlying causes of allograft rejection. Video Abstract.

Atelectrauma can be avoided if expiration is sufficiently brief: evidence from inverse modeling and oscillometry during airway pressure release ventilation.

BACKGROUND: Airway pressure release ventilation (APRV) has been shown to be protective against atelectrauma if expirations are brief. We hypothesize that this is protective because epithelial surfaces are not given enough time to come together and adhere during expiration, thereby avoiding their highly damaging forced separation during inspiration. METHODS: We investigated this hypothesis in a porcine model of ARDS induced by Tween lavage. Animals were ventilated with APRV in 4 groups based on whether inspiratory pressure was 28 or 40 cmH2O, and whether expiration was terminated when end-expiratory flow reached either 75% (a shorter expiration) or 25% (a longer expiration) of its initial peak value. A mathematical model of respiratory system mechanics that included a volume-dependent elastance term characterized by the parameter E 2 was fit to airway pressure-flow data obtained each hour for 6 h post-Tween injury during both expiration and inspiration. We also measured respiratory system impedance between 5 and 19 Hz continuously through inspiration at the same time points from which we derived a time-course for respiratory system resistance ( R rs ). RESULTS: E 2 during both expiration and inspiration was significantly different between the two longer expiration versus the two shorter expiration groups (ANOVA, p < 0.001). We found that E 2 was most depressed during inspiration in the higher-pressure group receiving the longer expiration, suggesting that E 2 reflects a balance between strain stiffening of the lung parenchyma and ongoing recruitment as lung volume increases. We also found in this group that R rs increased progressively during the first 0.5 s of inspiration and then began to decrease again as inspiration continued, which we interpret as corresponding to the point when continuing derecruitment was reversed by progressive lung inflation. CONCLUSIONS: These findings support the hypothesis that sufficiently short expiratory durations protect against atelectrauma because they do not give derecruitment enough time to manifest. This suggests a means for the personalized adjustment of mechanical ventilation.

Less Is (Sometimes) More: Laparoscopic Peritoneal Lavage and Drainage for Diverticulitis.

Introduction: Laparoscopic lavage and drainage (LLD) emerged as an alternative to Hartmann's procedure (HP) for patients with diverticulitis and uncontained perforation. Although initially popular as a less invasive approach, its use in modern practice is in question. This summary will review the available literature to show techniques, outcomes, and indications. Methods: The literature was reviewed for relevant case studies, randomized trials, prospective series, retrospective analyses, and meta-analyses to define peritoneal lavage and determine the clinical outcomes of peritoneal lavage. Results: LLD can be considered on an individual basis for Hinchey III diverticulitis (purulent peritonitis), but there are several contraindications. The extent of adhesionolysis (limited versus extensive) as well as the management of sites of perforation found during surgery are debated. Most surgeons continue lavage with warm saline until water runs clear and place drains in the operation. Three randomized controlled trials (RCTs), the LADIES, SCANDIV, and DILALA trials compared LLD with either resection and anastomosis or Hartmann's procedure. One other RCT (the LapLAND trial) is still with results pending. The LADIES trial studied LLD versus primary anastomosis and resection in Hinchey III diverticulitis and was terminated early secondary to higher 30-day morbidity in the LLD arm; however, 3-year data showed no significant difference in morbidity and mortality. The SCANDIV trial compared LLD with resection in acute diverticulitis (Hinchey I-III) and saw no difference in 90-day morbidity or mortality; however, it noted higher rates of reoperation in the LLD group. The DILALA trial compared Hinchey III diverticulitis patients undergoing LLD with open HP and found that the LLD group had a lower rate of reoperation at 2 years, but no difference in rates of readmission or mortality. Conclusions: Debate still remains over the technique of LLD and specific indications, as well as outcomes compared with resection and primary anastomosis or HP.