Chronic Suppurative Lung Disease Research Articles

The Respiratory Microbiome in Paediatric Chronic Wet Cough: What Is Known and Future Directions.

Chronic wet cough for longer than 4 weeks is a hallmark of chronic suppurative lung diseases (CSLD), including protracted bacterial bronchitis (PBB), and bronchiectasis in children. Severe lower respiratory infection early in life is a major risk factor of PBB and paediatric bronchiectasis. In these conditions, failure to clear an underlying endobronchial infection is hypothesised to drive ongoing inflammation and progressive tissue damage that culminates in irreversible bronchiectasis. Historically, the microbiology of paediatric chronic wet cough has been defined by culture-based studies focused on the detection and eradication of specific bacterial pathogens. Various 'omics technologies now allow for a more nuanced investigation of respiratory pathobiology and are enabling development of endotype-based models of care. Recent years have seen substantial advances in defining respiratory endotypes among adults with CSLD; however, less is understood about diseases affecting children. In this review, we explore the current understanding of the airway microbiome among children with chronic wet cough related to the PBB-bronchiectasis diagnostic continuum. We explore concepts emerging from the gut-lung axis and multi-omic studies that are expected to influence PBB and bronchiectasis endotyping efforts. We also consider how our evolving understanding of the airway microbiome is translating to new approaches in chronic wet cough diagnostics and treatments.

Chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand: TSANZ position statement summary.

Chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand: TSANZ position statement summary.

Associated Risk Factors and Diagnostic Value of Fiberoptic Bronchoscopy for Protracted Bacterial Bronchitis in Children.

Untreated protracted bacterial bronchitis (PBB), a chronic wet cough prevalent in children, may lead to chronic suppurative lung disease. However, clinical diagnostic criteria are currently nonspecific; thus, PBB may be misdiagnosed. Thus, we assessed the diagnostic value of fiberoptic bronchoscopy (FOB) and the risk factors associated with PBB. Children with chronic cough at The First Affiliated Hospital of Anhui Medical University from January 2015 to May 2020 were enrolled and allocated to a suspected PBB (n = 141) or a non-PBB (n = 206) group. All children underwent extensive laboratory, chest imaging, and allergen tests. Children with suspected PBB underwent FOB with bronchoalveolar lavage; lavage and sputum samples were cultured. All 347 children had a chronic wet cough for approximately 2 months. Of 141 children with suspected PBB, 140 received FOB with bronchoalveolar lavage. Visible tracheal changes included pale mucosa, mucosal congestion, edema, swelling, and increased secretions attached to the wall. Sputum was visible primarily in the left main bronchus (78.7%), left lower lobe (59.6%), right upper lobe (62.4%), and right lower lobe (64.5%). Sputum properties and amounts significantly differed between children with vs. without PBB (P < 0.05). Dermatophagoides (odds ratio (OR), 2.642; 95% CI, 1.283-5.369), milk protein (OR, 2.452; 95% CI, 1.243-4.836) allergies, and eczema (OR, 1.763; 95% CI, 1.011-3.075) were risk factors significantly associated with PBB. Dermatophagoides, milk protein, and eczema were associated with an increased risk of PBB. Sputum distribution and tracheal wall changes observed through FOB may distinguish PBB and assist in its diagnosis.

Diagnostic value of nasal nitric oxide for children with primary ciliary dyskinesia

Objective: To evaluate the value of nasal nitric oxide (nNO) measurement as a diagnostic tool for Chinese patients with primary ciliary dyskinesia (PCD). Methods: This study is a retrospective study. The patients were recruited from those who were admitted to the respiratory Department of Respiratory Medicine, Children's Hospital of Fudan University from March 2018 to September 2022. Children with PCD were included as the PCD group, and children with situs inversus or ambiguus, cystic fibrosis (CF), bronchiectasis, chronic suppurative lung disease and asthma were included as the PCD symptom-similar group. Children who visited the Department of Child health Care and urology in the same hospital from December 2022 to January 2023 were selected as nNO normal control group. nNO was measured during plateau exhalation against resistance in three groups. Mann-Whitney U test was used to analyze the nNO data. The receiver operating characteristic of nNO value for the diagnosis of PCD was plotted and, the area under the curve and Youden index was calculated to find the best cut-off value. Results: nNO was measured in 40 patients with PCD group, 75 PCD symptom-similar group (including 23 cases of situs inversus or ambiguus, 8 cases of CF, 26 cases of bronchiectasis or chronic suppurative lung disease, 18 cases of asthma), and 55 nNO normal controls group. The age of the three groups was respectively 9.7 (6.7,13.4), 9.3 (7.0,13.0) and 9.9 (7.3,13.0) years old. nNO values were significantly lower in children with PCD than in PCD symptom-similar group and nNO normal controls (12 (9,19) vs. 182 (121,222), 209 (165,261) nl/min, U=143.00, 2.00, both P<0.001). In the PCD symptom-similar group, situs inversus or ambiguus, CF, bronchiectasis or chronic suppurative lung disease and asthma were significantly higher than children with PCD (185 (123,218), 97 (52, 132), 154 (31, 202), 266 (202,414) vs. 12 (9,19) nl/min,U=1.00, 9.00, 133.00, 0, all P<0.001). A cut-off value of 84 nl/min could provide the best sensitivity (0.98) and specificity (0.92) with an area under the curve of 0.97 (95%CI 0.95-1.00, P<0.001). Conclusions: nNO value can draw a distinction between patients with PCD and others. A cut-off value of 84 nl/min is recommended for children with PCD.

Chronic Suppurative Lung Disease in Children: A Case Based Approach.

Bronchiectasis is a pathologic state of conducting airways manifested radiographically by evidence of bronchial dilation and clinically by chronic productive cough. Considered an "orphan disease" for long, it remains a major contributor to morbidity and mortality in both developed and underdeveloped countries. With the advances in the medical field accompanied by widespread access to vaccines and antibiotics, improved health services and better access to nutrition, the incidences of bronchiectasis have markedly decreased, particularly in developed countries. This review summarizes the current knowledge pertaining to the clinical definition, etiology, clinical approach and management related to pediatric bronchiectasis.

Pathogenesis of nontypeable Haemophilus influenzae infections in chronic suppurative lung disease.

The respiratory tract antimicrobial defense system is a multilayered defense mechanism that relies upon mucociliary clearance and components of both the innate and adaptive immune systems to protect the lungs from inhaled or aspirated microorganisms. One of these potential pathogens, nontypeable Haemophilus influenzae (NTHi), adopts several, multifaceted redundant strategies to successfully colonize the lower airways and establish a persistent infection. NTHi can impair mucociliary clearance, express multiple multifunctional adhesins for various cell types within the respiratory tract and evade host defenses by surviving within and between cells, forming biofilms, increasing antigenic drift, secreting proteases and antioxidants, and by host-pathogen cross-talk, impair macrophage and neutrophil function. NTHi is recognized as an important pathogen in several chronic lower respiratory disorders, such as protracted bacterial bronchitis, bronchiectasis, cystic fibrosis, and primary ciliary dyskinesia. The persistence of NTHi in human airways, including its capacity to form biofilms, results in chronic infection and inflammation, which can ultimately injure airway wall structures. The complex nature of the molecular pathogenetic mechanisms employed by NTHi is incompletely understood but improved understanding of its pathobiology will be important for developing effective therapies and vaccines, especially given the marked genetic heterogeneity of NTHi and its possession of phase-variable genes. Currently, no vaccine candidates are ready for large phase III clinical trials.

Personalising airway clearance in chronic suppurative lung diseases: a scoping review.

Personalised airway clearance techniques are commonly recommended to augment mucus clearance in chronic suppurative lung diseases. It is unclear what current literature tells us about how airway clearance regimens should be personalised. This scoping review explores current research on airway clearance technique in chronic suppurative lung diseases, to establish the extent and type of guidance in this area, identify knowledge gaps and determine the factors which physiotherapists should consider when personalising airway clearance regimens. Systematic searching of online databases (MEDLINE, EMBASE, CINAHL, PEDro, Cochrane, Web of Science) was used to identify full-text publications in the last 25 years that described methods of personalising airway clearance techniques in chronic suppurative lung diseases. Items from the TIDieR framework provided a priori categories which were modified based on the initial data to develop a "Best-fit" framework for data charting. The findings were subsequently transformed into a personalisation model. A broad range of publications were identified, most commonly general review papers (44%). The items identified were grouped into seven personalisation factors: physical, psychosocial, airway clearance technique (ACT) type, procedures, dosage, response and provider. As only two divergent models of ACT personalisation were found, the personalisation factors identified were then used to develop a model for physiotherapists. The personalisation of airway clearance regimens is widely discussed in the current literature, which provides a range of factors that should be considered. This review summarises the current literature, organising findings into a proposed airway clearance personalisation model, to provide clarity in this field.

Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand.

This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim.

Phage Therapy Administration Route, Regimen, and Need for Supplementary Antibiotics in Patients with Chronic Suppurative Lung Disease.

Antimicrobial resistance is leading to increased mortality, posing risk to those with chronic suppurative lung disease (CSLD). One therapeutic option may be to target treatment-resistant bacteria using viruses (bacteriophages [phages]). Currently, patients receiving phage therapy on compassionate grounds may not be receiving optimal treatment as there is no defined approach for phage use. This review aims to explore administration route, regimen, and need for supplementary antibiotics in phage therapy to treat bacterial infection in CSLD. Twelve articles totaling 18 participants included details of numerous phage administration routes with varying regimens. All articles reported an initial reduction of bacterial load or an improvement in patient symptoms, highlighting the potential of phage therapy in CSLD. Fifteen out of 18 used supplementary antibiotics. Standardized protocols informed by high-quality research are necessary to ensure safe and effective phage therapy. In the interim, systematic recording of information within case reports may be useful.

Clinical Course of Children with Chronic Suppurative Lung Disease or Bronchiectasis Infected with Pseudomonas aeruginosa.

Children with chronic wet cough and without cystic fibrosis (non-CF) may suffer from chronic suppurative lung disease (CSLD) or bronchiectasis. Pseudomonas aeruginosa (Pa) can be one of the offending microbes in these children. The present study aimed to describe the clinical course of children with the above two conditions who were infected with Pa. Data of 54 children with CSLD/bronchiectasis who were diagnosed and attended in our department were retrospectively analysed through a Cox proportional hazard model, with age, presence of bronchiectasis, use of inhaled colistin, azithromycin, inhaled hypertonic saline as the covariates. In 42 of the 54 patients, there was no identifiable cause or underlying chronic disorder. Microbiological clearance was defined as the absence of daily wet cough for four months along with four negative cultures taken during the last four consecutive follow-up visits. Multivariate analysis was performed with a Cox proportional hazard model with time to microbiological clearance as the outcome. Results are described as Hazard Ratios (HR) with 95% Confidence Intervals (95%CI). Nebulised antibiotics and the presence of bronchiectasis were statistically significant predictors of remission (HR: 3.99; 95%CI: 1.12-14.14; p = 0.032, and HR: 0.24; 95%CI: 0.08-0.71; p = 0.010). In conclusion, the rate of microbiological clearance increases with the use of inhaled colistin and decreases when there is established bronchiectasis.

Prevalence of chronic respiratory diseases in Aboriginal children: A whole population study.

The burden of bronchiectasis is disproportionately high in Aboriginal adults, with early mortality. Bronchiectasis precursors, that is, protracted bacterial bronchitis (PBB) and chronic suppurative lung disease (CSLD), often commence in early childhood. We previously reported a 10% prevalence of PBB in Aboriginal children aged 0 to 7 years, however there are no data on prevalence of chronic lung diseases in older children. Our study aimed to determine the prevalence of PBB, CSLD, bronchiectasis, and asthma in Aboriginal children living in four communities. A whole-population cross-sectional community co-designed study of Aboriginal children aged <18-years in four remote communities in Western Australia across two-time points, a month apart. Children were assessed by pediatric respiratory clinicians with spirometry undertaken (when possible) between March-September 2021. Children with respiratory symptoms were followed up via medical record audit from either the local medical clinic or via a respiratory specialist clinic through to March 2022 to establish a final diagnosis. We recruited 392 (91.6%) of those in the selected communities; median age = 8.4 years (interquartile range[IQR] 5.1-11.5). Seventy children (17.9%) had a chronic respiratory pathology or abnormal spirometry results. PBB was confirmed in 30 (7.7%), CSLD = 13 (3.3%), bronchiectasis = 5 (1.3%) and asthma = 17 (4.3%). The prevalence of chronic wet cough significantly increased with increasing age. The prevalence of PBB, CSLD and bronchiectasis is high in Aboriginal children and chronic wet cough increases with age. This study highlights the high disease burden in Aboriginal children and the urgent need for strategies to address these conditions.

Mucolytics for children with chronic suppurative lung disease

Mucolytics for children with chronic suppurative lung disease

An invisible threat? Aspergillus positive cultures and co-infecting bacteria in airway samples

BackgroundAspergillus fumigatus (Af) infection is associated with poor lung health in chronic suppurative lung diseases but often goes undetected. We hypothesised that inhibition of Af growth by Pseudomonas aeruginosa (Pa) increases the frequency of false-negative Af culture in co-infected people. Using a substantial group of cystic fibrosis (CF) airway samples, we assessed the relationship between Af and bacterial pathogens, additionally comparing fungal culture with next-generation sequencing. MethodsFrequency of co-culture was assessed for 44,554 sputum/BAL cultures, from 1,367 CF patients between the years 2010–2020. In a subgroup, Internal Transcribed Spacer-2 (ITS2) fungal sequencing was used to determine sequencing-positive, culture-negative (S+/C-) rates. ResultsPa+ samples were nearly 40% less likely (P<0.0001) than Pa- samples to culture Af, an effect that was also seen with some other Gram-negative isolates. This impact varied with Pa density and appeared to be moderated by Staphylococcus aureus co-infection. Sequencing identified Af-S+/C- for 40.1% of tested sputa. Samples with Pa had higher rates of Af-S+/C- (49.3%) than those without (35.7%; RR 1.38 [1.02–1.93], P<0.05). Af-S+/C- rate was not changed by other common bacterial infections. Pa did not affect the S+/C- rates of Candida, Exophiala or Scedosporium. ConclusionsPa/ Af co-positive cultures are less common than expected in CF. Our findings suggest an Af-positive culture is less likely in the presence of Pa. Interpretation of negative cultures should be cautious, particularly in Pa-positive samples, and a companion molecular diagnostic could be useful. Further work investigating mechanisms, alternative detection techniques and other chronic suppurative lung diseases is needed.

Pulmonary Function Tests in Childhood Asthma: Which indices are Better for Assessment of Severity?

To study pulmonary function tests in childhood asthma and to determine which indices are better for assessment of severity. This was a hospital-based, cross-sectional study. All consecutive children aged between 5 and 15 y with mild and severe persistent asthma were enrolled. Children in whom diagnosis of asthma was doubtful and those with chronic lung disease or suppurative lung disease were excluded. Diagnosis and classification was based on GINA guidelines. Age-/sex-matched controls who did not have history of wheezing any time in the past were selected. Detailed spirometry was performed on all children enrolled using RMS HELIOS 401. A total of 144 children were enrolled in the study (48 children in each group, i.e., control, mild and severe). Mean age of the study population was 9.06 ± 2.604 y with M:F ratio of 1.9:1. Mean percent of predicted values of FEV1, FVC, FEV1/FVC, FEF25-75, and PEFR in the control group was 94.83, 92.63, 103.25, 73.90, and 93.60; in the mild group was 90.58, 83.52, 111.10, 76.50, and 92.00; and in the severe group 57.56, 62.83, 92.85, 40.15, and 62.12, respectively. Values of all the indices decreased with increase in severity. FEV1 (95% CI: 0.884to0.971) having the highest correlation coefficient (-0.652) with respect to severity of asthma and FEV1/FVC having the least (-0.202). FEF25-75 (95% CI: 0.652 to 0.803) having a higher area under the curve, was a better spirometric parameter in predicting mild asthma. FEV1 was better index for assessing severity of asthma and FEF25-75 better in predicting mild asthma.

The Predictive Role of Psychological Status and Disease Severity Indexes on Quality of Life Among Patients with Non-CF Bronchiectasis.

Bronchiectasis is a chronic suppurative lung disease that significantly impacts the patients' quality of life. Aim of this study is to evaluate the relationship between life of quality and patient's psychological status and bronchiectasis disease severity indexes in patients with non-Cystic Fibrosis (CF) bronchiectasis. We also aimed to investigate the validity and reliability of Turkish version of Quality-of-Life Questionnaire-Bronchiectasis (QoL-B V3.1) in Turkish adult bronchiectatic patients. 90 stable non-CF bronchiectatic adult patients were enrolled into this study. At baseline, dyspnea score, BMI, lung function tests, sputum cultures, number of exacerbations and hospital admissions, disease severity indexes were recorded. All of the participants underwent quality of life assessment using both QoL-B V3.1 and of Short-Form (SF)-36 questionnaires, psychological status was evaluated by using HADS (Hospital Anxiety and Depression Scale). In all study participants, anxiety was diagnosed in 27/90 (30%) of patients and depression was diagnosed in 37/90 (41%) of patients. Patients with anxiety and depression had lower quality of life scores in various domains (p:0.026-p:0.001) and HADS scores negatively correlated with several quality-of-life domains (r=-0.216 - r=- 0.343). Female patients had higher risk for depression (55% vs 22%, p:0.002) and worse quality of life than males (p:0.016-p:0.038). Several life quality scores of both instruments were worse in patients with moderate-severe disease severity indexes when compared with those of mild groups. Moreover, Turkish version of newly described QoL-B V3.1 questionnaire was found to be reliable and valid instrument to evaluate the quality of life. These results emphasize the importance of mental health and disease severity as significant determinants of the life quality in patients particularly female patients with non-CF bronchiectasis.

The Predictive Role of Psychological Status and Disease Severity Indexes on Quality of Life Among Patients with Non-CF Bronchiectasis

Objective Bronchiectasis is a chronic suppurative lung disease that significantly impacts the patients’ quality of life. The aim of this study is to evaluate the relationship between quality of life and patient’s psychological status and bronchiectasis disease severity indexes in patients with non-cystic fibrosis bronchiectasis. We also aimed to investigate the validity and reliability of Turkish version of Quality of Life Questionnaire-Bronchiectasis (V3.1) in Turkish adult bronchiectatic patients.MATERIAL AND Methods In total, 90 stable non-cystic fibrosis bronchiectatic adult patients were enrolled in this study. At baseline, dyspnea score, body mass index, lung function tests, sputum cultures, number of exacerbations and hospital admissions, and disease severity indexes were recorded. All of the participants underwent quality of life assessment using both Quality of Life Questionnaire-Bronchiectasis V3.1 and Short Form-36 questionnaires, and psychological status was evaluated by using Hospital Anxiety and Depression Scale.Results In all study participants, anxiety was diagnosed in 27/90 (30%) of patients, and depression was diagnosed in 37/90 (41%) of patients. Patients with anxiety and depression had lower quality of life scores in various domains (P = .026-.001), and Hospital Anxiety and Depression Scale scores negatively correlated with several quality of life domains (r = −0.216 to 0.343). Female patients had higher risk for depression (55% vs 22%, P = .002) and worse quality of life than males (P = .016-.038). Several life quality scores of both instruments were worse in patients with moderate–severe disease severity indexes when compared with those of mild groups. Moreover, Turkish version of newly described Quality of Life Questionnaire-Bronchiectasis V3.1 questionnaire was found to be a reliable and valid instrument to evaluate the quality of life.Conclusion These results emphasize the importance of mental health and disease severity as significant determinants of the life quality in patients, particularly female patients with non-cystic fibrosis bronchiectasis.

Comparison of the airway microbiota in children with chronic suppurative lung disease

RationaleThe airway microbiota is important in chronic suppurative lung diseases, such as primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). This comparison has not previously been described but is important...

Utility of a personalised Bronchiectasis Action Management Plan (BAMP) for children with bronchiectasis: protocol for a multicentre, double-blind parallel, superiority randomised controlled trial

IntroductionBronchiectasis is no longer considered rare or irreversible in children, yet it remains relatively under-researched and neglected in respiratory health globally. Bronchiectasis (including chronic suppurative lung disease) causes substantial morbidity...

Fissure adjacent partial lobe atelectasis in primary ciliary dyskinesia.

Establishing the underlying cause in a child with chronic suppurative lung disease (CSLD) allows for targeted treatment and screening for associated complications. One cause of CSLD is primary ciliary dyskinesia (PCD). Testing for PCD requires specialist expertise which is not widely available. Computed tomography (CT) scans are commonly performed when assessing CSLD. Identifying PCD-specific signs on CT would help clinicians in deciding when to refer for specialist testing. One potential PCD-specific sign we have observed is fissure adjacent partial lobe atelectasis (FAPLA). We aimed to assess if FAPLA is commonly found in CT of PCD patients. Fifty-eight CT scans from 42 adult and child PCD patients were analysed. The presence and distribution of FAPLA were noted, and its association to sputum culture and other signs commonly seen in CSLD (bronchiectasis, bronchial wall thickening, air trapping and mucus plugging). FAPLA was found in 13 of 40 participants in their earliest CT scan. The prevalence of FAPLA was similar in children and adults. FAPLA involved the right middle lobe in all 13 cases and was systematically associated with ≥1 other structural change. There was no association between FAPLA and bacterial isolation from sputum. FAPLA was found in 32.5% PCD scans, without difference between children and adults in terms of frequency. Future work will determine if it is a PCD-specific sign by assessing whether it is also found in other CSLD processes and analysing more scans from children with PCD to determine how early this sign develops.

Clinical impact of respiratory virus in pulmonary exacerbations of children with Cystic Fibrosis

Cystic Fibrosis (CF) is a genetic, multisystemic, progressive illness that causes chronic suppurative lung disease. A major cause of morbimortality in this condition are pulmonary exacerbations. Although classically attributed to bacterial infections, respiratory virus have been increasingly recognized in its ethiopathogeny. Nasopharyngeal swab samples were collected from children < 18 years old with CF in Rio de Janeiro, Brazil, with pulmonary exacerbation criteria. Samples were submitted to RT-PCR for Adenovirus, Influenza A and B, Parainfluenza Virus, Respiratory Syncytial Virus (RSV), Metapneumovirus and Rhinovirus. Virus positive and virus negative groups were compared in regards to clinical presentation, severity of exacerbation and bacterial colonization. Out of 70 samples collected from 48 patients, 35.7% were positive for respiratory viruses. Rhinovirus were the most common (28% of all positive samples), followed by RSV. The virus positive group was associated with change in sinus discharge (p = 0.03). Considering only patients younger than five years old, positive virus detection was also associated with fever (p = 0.01). There was no significant difference in clinical severity or in bacterial colonization between virus positive and negative groups. Prospective studies are still needed to assess the long term impact of viral infections in patients with CF, and their interaction with the bacterial microbiome in these patients.