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INTRODUCTION: Non-tuberculous mycobacteria (NTM) are increasingly isolated in individuals with presumed/confirmed pulmonary TB. We aimed to estimate the prevalence and species distribution of NTM among presumed/confirmed drug-resistant TB (DR-TB) individuals and determine NTM isolation predictors. METHODS: Sputum samples collected for DR-TB diagnosis and follow-up from 2012 to 2021 in Ghana were retrospectively analysed. Samples were subjected to sputum smear microscopy (SSM) and mycobacterial culture. The MPT64 assay was performed on positive cultures to distinguish between Mycobacterium tuberculosis complex MTBc and NTM. NTM isolates were re-cultured for species identification using GenoType® Mycobacterium CM/AS line-probe assay, polymerase chain reaction, and Sanger sequencing targeting 16S rRNA and rpoB genes. MTBc isolates identified by GenoType underwent spoligotyping. A logistic regression model was used to identify the predictors of NTM isolation. RESULTS: Of the 2,492 samples, 839 (33.7%) tested culture-positive for mycobacteria, with 257 (30.6%) presumed to be NTM. Of these, 53 (23.6%) were identified at the species level, with a predominance of M. intracellulare (66.0%). MPT64 testing missed 18 (3%) MTBc isolates. Logistic regression showed increased odds of NTM isolation in follow-up samples (aOR 2.41, 95% CI 1.46-3.99). NTM species were isolated from 46 patients, with four classified as NTM pulmonary disease. CONCLUSION: Enhancing our understanding of local NTM epidemiology and improving local diagnostic capabilities can optimise patient management strategies and outcomes.
INTRODUCTION: Les mycobactéries non tuberculeuses (NTM) sont de plus en plus souvent isolées chez les personnes atteintes de TB pulmonaire présumée/confirmée (DR-TB). Notre étude visait à évaluer la fréquence et la répartition des différentes espèces de NTM chez les personnes atteintes de TB pharmacorésistante, ainsi qu'à identifier les facteurs prédictifs de l'isolement de ces NTM. MÉTHODES: Les échantillons d'expectorations collectés entre 2012 et 2021 au Ghana pour le diagnostic et le suivi de la DR-TB ont été analysés rétrospectivement. Les échantillons ont subi une microscopie du frottis d'expectoration (SSM) et une culture mycobactérienne. Le test MPT64 a été réalisé sur les cultures positives pour différencier le complexe Mycobacterium tuberculosis (MTBc) et les NTM. Les isolats de NTM ont été soumis à une nouvelle culture pour identification des espèces à l'aide du test par sondes en ligne GenoType® Mycobacterium CM/AS, de l'amplification en chaîne par polymérase et du séquençage de Sanger ciblant les gènes 16S rRNA et rpoB. Les isolats de MTBc identifiés par GenoType ont été soumis à un spoligotypage. Un modèle de régression logistique a été utilisé pour identifier les facteurs prédictifs de l'isolement des NTM. RÉSULTATS: Parmi les 2 492 échantillons analysés, 839 (33,7%) ont été testés positifs à la culture de mycobactéries, dont 257 (30,6%) étaient présumés être des NTM. Parmi ces échantillons, 53 (23,6%) ont été identifiés au niveau de l'espèce, avec une prédominance de M. intracellulare (66,0%). Le test MPT64 a échoué à détecter 18 (3%) isolats de MTBc. L'analyse de régression logistique a révélé une probabilité accrue d'isolement de MNT dans les échantillons de suivi (aOR 2,41 ; IC à 95% 1,463,99). Des espèces de NTM ont été isolées chez 46 patients, dont quatre ont été classés dans la catégorie des maladies pulmonaires à NTM. CONCLUSION: Une connaissance approfondie de l'épidémiologie locale des NTM et le renforcement des compétences de diagnostic au niveau local peuvent améliorer les stratégies de prise en charge des patients et les résultats obtenus.
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OBJECTIVE: Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is caused by an imbalance between pathogens and impaired host immune responses. Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) are the two major pathogens that cause NTM-PD. In this study, we sought to dissect the transcriptomes of peripheral blood immune cells at the single-cell resolution in NTM-PD patients and explore potential clinical markers for NTM-PD diagnosis and treatment. METHODS: Peripheral blood samples were collected from six NTM-PD patients, including three MAB-PD patients, three MAC-PD patients, and two healthy controls. We employed single-cell RNA sequencing (scRNA-seq) to define the transcriptomic landscape at a single-cell resolution. A comprehensive scRNA-seq analysis was performed, and flow cytometry was conducted to validate the results of scRNA-seq. RESULTS: A total of 27,898 cells were analyzed. Nine T-cells, six mononuclear phagocytes (MPs), and four neutrophil subclusters were defined. During NTM infection, naïve T-cells were reduced, and effector T-cells increased. High cytotoxic activities were shown in T-cells of NTM-PD patients. The proportion of inflammatory and activated MPs subclusters was enriched in NTM-PD patients. Among neutrophil subclusters, an IFIT1+ neutrophil subcluster was expanded in NTM-PD compared to healthy controls. This suggests that IFIT1+ neutrophil subcluster might play an important role in host defense against NTM. Functional enrichment analysis of this subcluster suggested that it is related to interferon response. Cell-cell interaction analysis revealed enhanced CXCL8-CXCR1/2 interactions between the IFIT1+ neutrophil subcluster and NK cells, NKT cells, classical mononuclear phagocytes subcluster 1 (classical Mo1), classical mononuclear phagocytes subcluster 2 (classical Mo2) in NTM-PD patients compared to healthy controls. CONCLUSIONS: Our data revealed disease-specific immune cell subclusters and provided potential new targets of NTM-PD. Specific expansion of IFIT1+ neutrophil subclusters and the CXCL8-CXCR1/2 axis may be involved in the pathogenesis of NTM-PD. These insights may have implications for the diagnosis and treatment of NTM-PD.
Subject(s)
Adaptor Proteins, Signal Transducing , Neutrophils , RNA-Binding Proteins , Single-Cell Analysis , Transcriptome , Humans , Neutrophils/immunology , RNA-Binding Proteins/genetics , RNA-Binding Proteins/immunology , Male , Middle Aged , Female , Adaptor Proteins, Signal Transducing/genetics , Mycobacterium Infections, Nontuberculous/immunology , Mycobacterium Infections, Nontuberculous/blood , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium avium Complex/immunology , Aged , Mycobacterium abscessus/immunology , T-Lymphocytes/immunology , AdultABSTRACT
While the incidence and prevalence of non-tuberculous mycobacterial-pulmonary disease (NTM-PD) are increasing and microscopic polyangiitis (MPA) is common in East Asian countries, case reports of MPA associated with NTM-PD are limited. A 72-year-old male receiving treatment for NTM-PD with antibiotics was referred to our hospital with fever and arthralgia that developed a few months previously. A blood test revealed the presence of the myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) and renal impairment. Based on a pathological examination of renal tissue, which showed crescentic glomerulonephritis, the patient was diagnosed with MPA. Due to acute kidney injury and strongly positive MPO-ANCA, pulse steroid therapy was initiated followed by intravenous rituximab (RTX). The patient also received plasmapheresis (14 sessions). Renal dysfunction was reversed. MPA associated with NTM-PD is extremely rare and, thus, there is currently no established treatment. Our patient was diagnosed with MPA based on the findings of renal biopsy while receiving treatment for NTM-PD. RTX and plasmapheresis combined with systemic glucocorticoid therapy were initiated before these clinical conditions had fully recovered. Although MPA secondary to NTM-PD may be more refractory to treatment than primary MPA in the presence of a very low interferon-gamma (IFN-γ) level, this case was successfully treated with steroids, RTX, and plasmapheresis.
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BACKGROUND: Wearing facemasks in public is effective in preventing viral transmission. However, no study has evaluated the impact of wearing facemasks during exercise on dyspnea in patients with chronic pulmonary infections from multifaceted aspects, including sensory qualities and emotional responses. The aim of this study was to evaluate facemask-related dyspnea during exercise in this patient population. METHODS: We conducted a randomized crossover study involving adult patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) or bronchiectasis who participated in exercise sessions, both with (mask-on) and without (mask-off) surgical facemasks. The sensory and emotional dimensions of dyspnea during each exercise session were assessed using the Multidimensional Dyspnea Profile. Statistical analyses were performed to identify factors associated with worsening scores for each dimension. RESULTS: Thirty-four patients (mean age [standard deviation]: 71.6 [8.6] years) were included in the analysis. The median [interquartile range] total scores for the sensory and emotional dimensions of dyspnea were 3.5 [1, 9.5] (mask-off) vs. 10 [5.5, 23.8] (mask-on) (P < 0.001) and 0 [0, 5] (mask-off) vs. 3 [0.8, 10.3] (mask-on) (P = 0.115), respectively. "Air hunger" was the primary sensory descriptor of mask-related dyspnea. Vital capacity (VC) < 80% of the predicted value was a significant risk factor for worsening sensory dimension scores when wearing masks (odds ratio [95% confidence interval]: 5.5 [1.16-26.1], P = 0.038). CONCLUSIONS: The findings of this study indicate that patients with NTM-PD or bronchiectasis, particularly those with VC <80% of the predicted value, are likely to experience the sensory dimension of dyspnea during exercise while wearing surgical facemasks.
Subject(s)
Bronchiectasis , Pneumonia , Adult , Humans , Child , Masks/adverse effects , Cross-Over Studies , Dyspnea/etiology , Pneumonia/complications , Bronchiectasis/complicationsABSTRACT
BACKGROUND: Although the incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing annually, it is easily misdiagnosed as pulmonary tuberculosis (PTB). This study aimed to screen and identify the immunological and radiological characteristics that differentiate NTM-PD from PTB and to construct a discriminatory diagnostic model for NTM-PD, providing new tools for its differential diagnosis. METHODS: Hospitalised patients diagnosed with NTM-PD or PTB between January 2019 and June 2023 were included in the study. Immunological and radiological characteristics were compared between the two groups. Based on the selected differential features, a logistic regression algorithm was used to construct a discriminatory diagnostic model for NTM-PD, and its diagnostic performance was preliminarily analysed. RESULTS: Patients with NTM-PD were significantly older than those with PTB and the tuberculosis-specific interferon-gamma release assay (TB-IGRA) positivity rate was significantly lower in the NTM-PD group. Moreover, the absolute counts of total T lymphocytes, CD4+ T lymphocytes, CD8+ T lymphocytes, NK cells, and B lymphocytes were significantly lower in patients with NTM-PD and PTB than in healthy controls. Additionally, patients with NTM-PD had a significantly lower absolute count of B lymphocytes than the PTB group. Radiological analysis revealed significant differences between patients with NTM-PD and PTB in terms of cavity wall thickness, bronchial dilation, lung consolidation, pulmonary nodule size, pulmonary emphysema, lung bullae, lymph node calcification, pleural effusion, mediastinal and hilar lymphadenopathy, and the tree-in-bud sign. Bronchial dilation was identified as the predominant risk factor of NTM-PD, whereas TB-IGRA positivity, lymph node calcification, pleural effusion, and mediastinal and hilar lymphadenopathies were protective factors. Based on this, we constructed a discriminatory diagnostic model for NTM-PD. Its receiver operating characteristic curve demonstrated good diagnostic performance, with an area under the curve of 0.938. At the maximum Youden index of 0.746, the sensitivity and specificity were 0.835 and 0.911, respectively. CONCLUSIONS: Patients with NTM-PD and PTB exhibited impaired humoral and cellular immune functions as well as significant differences in radiological features. The constructed NTM-PD diagnostic model demonstrated good diagnostic performance. This study provides a new tool for the differential diagnosis of NTM-PD.
Subject(s)
Lung Diseases , Mycobacterium Infections, Nontuberculous , Pleural Effusion , Tuberculosis, Pulmonary , Tuberculosis , Humans , Case-Control Studies , Diagnosis, Differential , Tuberculosis, Pulmonary/diagnostic imaging , Mycobacterium Infections, Nontuberculous/diagnostic imaging , Lung Diseases/diagnostic imaging , Nontuberculous Mycobacteria , Retrospective StudiesABSTRACT
Background: The incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased in recent years. However, the clinical and immunologic characteristics of NTM-PD patients have received little attention. Methods: NTM strains, clinical symptoms, underlying diseases, lung CT findings, lymphocyte subsets, and drug susceptibility tests (DSTs) of NTM-PD patients were investigated. Then, the counts of immune cells of NTM-PD patients and their correlation were evaluated using principal component analysis (PCA) and correlation analysis. Results: 135 NTM-PD patients and 30 healthy controls (HCs) were enrolled from 2015 to 2021 in a certain tertiary hospital in Beijing. The number of NTM-PD patients increased every year, and Mycobacterium intracellulare (M. intracellulare), M. abscessus, M. avium, and M. kansasii were the major pathogens of NTM-PD. The main clinical symptoms of NTM-PD patients were cough and sputum production, and the primary lung CT findings were thin-walled cavity, bronchiectasis, and nodules. In addition, we identified 23 clinical isolates from 87 NTM-PD patients with strain records. The DST showed that almost all of M. abscessus and M. avium and more than half of the M. intracellulare and M. avium complex groups were resistant to anti-tuberculosis drugs tested in this study. M. xenopi was resistant to all aminoglycosides. M. kansasii was 100% resistant to kanamycin, capreomycin, amikacin, and para-aminosalicylic acid, and sensitive to streptomycin, ethambutol, levofloxacin, azithromycin, and rifamycin. Compared to other drugs, low resistance to rifabutin and azithromycin was observed among NTM-PD isolates. Furthermore, the absolute counts of innate and adaptive immune cells in NTM-PD patients were significantly lower than those in HCs. PCA and correlation analysis revealed that total T, CD4+, and CD8+ T lymphocytes played an essential role in the protective immunity of NTM-PD patients, and there was a robust positive correlation between them. Conclusion: The incidence of NTM-PD increased annually in Beijing. Individuals with bronchiectasis and COPD have been shown to be highly susceptible to NTM-PD. NTM-PD patients is characterized by compromised immune function, non-specific clinical symptoms, high drug resistance, thin-walled cavity damage on imaging, as well as significantly reduced numbers of both innate and adaptive immune cells.
Subject(s)
Bronchiectasis , Lung Diseases , Mycobacterium Infections, Nontuberculous , Humans , Nontuberculous Mycobacteria , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/epidemiology , Follow-Up Studies , Tertiary Care Centers , Azithromycin , Lung Diseases/microbiology , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic useABSTRACT
Increased serum C-reactive protein (CRP) levels at the time of diagnosis predicted worse prognosis in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). Approximately one-quarter of the patients with NTM-PD had higher than normal CRP levels, and this elevation led to a higher risk of death.
Subject(s)
Lung Diseases , Mycobacterium Infections, Nontuberculous , Humans , Nontuberculous Mycobacteria , Prognosis , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/microbiology , Retrospective Studies , Lung Diseases/microbiology , BiomarkersABSTRACT
Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is an increasingly recognised global health issue. Studies have suggested that neutrophils may play an important role in controlling NTM infection and contribute to protective immune responses within the early phase of infection. However, these cells are also adversely associated with disease progression and exacerbation and can contribute to pathology, for example in the development of bronchiectasis. In this review, we discuss the key findings and latest evidence regarding the diverse functions of neutrophils in NTM infection. First, we focus on studies that implicate neutrophils in the early response to NTM infection and the evidence reporting neutrophils' capability to kill NTM. Next, we present an overview of the positive and negative effects that characterise the bidirectional relationship between neutrophils and adaptive immunity. We consider the pathological role of neutrophils in driving the clinical phenotype of NTM-PD including bronchiectasis. Finally, we highlight the current promising treatments in development targeting neutrophils in airways diseases. Clearly, more insights on the roles of neutrophils in NTM-PD are needed in order to inform both preventative strategies and host-directed therapy for these important infections.
Subject(s)
Bronchiectasis , Lung Diseases , Mycobacterium Infections, Nontuberculous , Humans , Nontuberculous Mycobacteria/physiology , Mycobacterium Infections, Nontuberculous/microbiology , Neutrophils , Lung Diseases/complications , Lung Diseases/microbiology , Bronchiectasis/complications , Bronchiectasis/microbiologyABSTRACT
Background: This study aimed (I) to investigate the clinical implication of computed tomography (CT) cavity volume in tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD), and (II) to develop a three-dimensional (3D) nnU-Net model to automatically detect and quantify cavity volume on CT images. Methods: We retrospectively included conveniently sampled 206 TB and 186 NTM-PD patients in a tertiary referral hospital, who underwent thin-section chest CT scans from 2012 through 2019. TB was microbiologically confirmed, and NTM-PD was diagnosed by 2007 Infectious Diseases Society of America/American Thoracic Society guideline. The reference cavities were semi-automatically segmented on CT images and a 3D nnU-Net model was built with 298 cases (240 cases for training, 20 for tuning, and 38 for internal validation). Receiver operating characteristic curves were used to evaluate the accuracy of the CT cavity volume for two clinically relevant parameters: sputum smear positivity in TB and treatment in NTM-PD. The sensitivity and false-positive rate were calculated to assess the cavity detection of nnU-Net using radiologist-detected cavities as references, and the intraclass correlation coefficient (ICC) between the reference and the U-Net-derived cavity volumes was analyzed. Results: The mean CT cavity volumes in TB and NTM-PD patients were 11.3 and 16.4 cm3, respectively, and were significantly greater in smear-positive TB (P<0.001) and NTM-PD necessitating treatment (P=0.020). The CT cavity volume provided areas under the curve of 0.701 [95% confidence interval (CI): 0.620-0.782] for TB sputum positivity and 0.834 (95% CI: 0.773-0.894) for necessity of NTM-PD treatment. The nnU-Net provided per-patient sensitivity of 100% (19/19) and per-lesion sensitivity of 83.7% (41/49) in the validation dataset, with an average of 0.47 false-positive small cavities per patient (median volume, 0.26 cm3). The mean Dice similarity coefficient between the manually segmented cavities and the U-Net-derived cavities was 78.9. The ICCs between the reference and U-Net-derived volumes were 0.991 (95% CI: 0.983-0.995) and 0.933 (95% CI: 0.897-0.957) on a per-patient and per-lesion basis, respectively. Conclusions: CT cavity volume was associated with sputum positivity in TB and necessity of treatment in NTM-PD. The 3D nnU-Net model could automatically detect and quantify mycobacterial cavities on chest CT, helping assess TB infectivity and initiate NTM-TB treatment.
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Although there has been a drastic decline in the cases of Tuberculosis in the United States, the prevalence of infections caused by Mycobacterium avium Complex (MAC) has steadily increased in the past decades. Mycobacterium avium (M. avium) is one of the most abundant microorganisms in the MAC species. The mycobacterium genus is divided into two major groups: tuberculosis causing mycobacteria and non-tuberculous mycobacteria. MAC is most prominent among the non-tuberculous mycobacteria. MAC is an opportunistic pathogen that is present in soil, water, and droplets in the air. MAC infections can result in respiratory disease and can disseminate in affected patients. MAC infections are especially prevalent in patients with preexisting respiratory conditions such as Chronic Obstructive Pulmonary Disease (COPD). COPD is one of the most common lung conditions in the world with the primary cause being smoking in developed countries. COPD involves chronic inflammation of lung tissue resulting in increased susceptibility to infection. There is a lack of research regarding the pathophysiology that leads COPD patients to be susceptible to MAC infection. Our review paper therefore aims to investigate how the pathogenicity of MAC bacteria and immune decline seen in COPD patients leads to a greater susceptibility to MAC infection among COPD patients.
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BACKGROUND: Nontuberculous mycobacterium (NTM) species are ubiquitous microorganisms. NTM pulmonary disease (NTM-PD) is thought to be caused not by human-to-human transmission but by independent environmental acquisition. However, recent studies using next-generation sequencing (NGS) have reported trans-continental spread of Mycobacterium abscessus among patients with cystic fibrosis. RESULTS: We investigated NTM genomes through NGS to examine transmission patterns in three pairs of co-habiting patients with NTM-PD who were suspected of patient-to-patient transmission. Three pairs of patients with NTM-PD co-habiting for at least 15 years were enrolled: a mother and a daughter with M. avium-PD, a couple with M. intracellulare-PD, and a second couple, one of whom was infected with M. intracellulare and the other of whom was infected with M. abscessus. Whole genome sequencing was performed using patients' NTM isolates as well as environmental specimens. Genetic distances were estimated based on single nucleotide polymorphisms (SNPs). By comparison with the genetic distances among 78 publicly available NTM genomes, NTM isolates derived from the two pairs of patients infected with the same NTM species were not closely related to each other. In phylogenetic analysis, the NTM isolates from patients with M. avium-PD clustered with isolates from different environmental sources. CONCLUSIONS: In conclusion, considering the genetic distances between NTM strains, the likelihood of patient-to-patient transmission in pairs of co-habiting NTM-PD patients without overt immune deficiency is minimal.
Subject(s)
Environmental Microbiology , Lung Diseases/microbiology , Nontuberculous Mycobacteria/genetics , Sputum/microbiology , Whole Genome Sequencing/methods , Aged , Aged, 80 and over , Cystic Fibrosis/microbiology , Female , Humans , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/transmission , Mycobacterium avium Complex/genetics , Mycobacterium avium Complex/isolation & purification , Nontuberculous Mycobacteria/classification , Nontuberculous Mycobacteria/physiology , PhylogenyABSTRACT
BACKGROUND/OBJECTIVES: Assessing the clinical relevance of non-tuberculous mycobacteria (NTM) isolated from respiratory samples can be challenging. The epidemiology and pathogenicity of NTM species vary geographically. We aimed to outline the clinical relevance and associated radiological patterns of NTM species isolated in Belgium. METHODS: We performed a retrospective multicentre analysis of all patients identified from the laboratory database with > 1 respiratory sample growing NTM from January 2010 through December 2017. We collected clinical, radiological and microbiological data through medical record review and assessed clinical relevance according to ATS/IDSA criteria for NTM pulmonary disease (NTM-PD). RESULTS: Of the 384 unique patients, 60% were male, 56% had a smoking history and 61% had pre-existing lung disease. Mycobacterium avium complex (MAC), M. gordonae and M. xenopi were the most frequently isolated species: 53, 15 and 8% respectively. 43% of patients met ATS/IDSA criteria, of whom 28% presented with fibrocavitary disease. Weight loss, fever, nodular bronchiectatic and fibrocavitary lesions on chest CT, and a positive acid-fast bacilli (AFB) stain were significantly associated with NTM-PD. The species with the highest pathogenic potential were M. abscessus (11/12), M. malmoense (6/7) and M. intracellulare (41/64). CONCLUSION: In our study, MAC was the most commonly isolated NTM species, but M. abscessus and M. malmoense showed the highest probability of being clinically relevant. Clinical relevance varied not only by species but also by radiological findings on chest CT and AFB staining. Clinicians should consider these elements in their treatment decision making. Prospective data including clinical outcome are needed to provide more robust evidence.
Subject(s)
Bronchiectasis/complications , Cystic Fibrosis/complications , Mycobacterium Infections, Nontuberculous/etiology , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium avium Complex/isolation & purification , Pulmonary Disease, Chronic Obstructive/complications , Aged , Belgium , Diagnostic Tests, Routine , Disease Susceptibility , Female , Humans , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Non-Tuberculous Mycobacterial-pulmonary disease (NTM-PD) is increasing in incidence and prevalence. Mycobacterium abscessus (M.abscessus) is a rapid growing multi-resistant NTM associated with severe NTM-PD requiring prolonged antibiotic therapy. Complications of therapy are common but reports on direct complications of active NTM-PD are rare. Vasculitis has been described as a rare complication of NTM-PD, most often in individuals with inherited immune defects. This case is the first to describe an ANCA positive vasculitide (Microscopic Polyangiitis) secondary to M.abscessus pulmonary disease. CASE PRESENTATION: A 70 year old female with bronchiectasis underwent a clinical decline associated with the growth of M.abscessus and was diagnosed with NTM-PD. Before treatment could be initiated she developed small joint arthralgia and a glove and stocking axonal loss sensorimotor neuropathy. Positive Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) and Myeloperoxidase-ANCA (MPO-ANCA) titres led to a diagnosis of microscopic polyangiitis. Further investigation revealed reduced interferon-gamma production but no other significant immune dysfunction. Dual treatment with immunosuppressive therapy (Corticosteroids/Cyclophosphamide) for vasculitis and antimicrobial therapy for M.abscessus NTM-PD was initiated. Clinical stability was difficult to achieve with reductions in immunosuppression triggering vasculitic flares. One flare led to retinal vein occlusion with impending visual loss requiring escalation in immunosuppression to Rituximab infusions. An increase in immunosuppression led to a deterioration in NTM-PD necessitating alterations to antibiotic regimes. Adverse effects including alopecia and Achilles tendonitis have further limited antibiotic choices resulting in a strategy of pulsed intra-venous therapy to stabilise NTM-PD. CONCLUSIONS: This is the first reported case of an ANCA positive vasculitis secondary to M.abscessus pulmonary disease. This rare but important complication had a significant impact on the patient adding to the complexity of an already significant disease and treatment burden. The potential role of reduced interferon-gamma production in this case highlights the importance of investigating immune function in those with mycobacterial infection and the intricate relationship between mycobacterial infection and immune dysfunction. Immune dysfunction caused by genetic defects or immunosuppressive therapy is a known risk factor for NTM-PD. Balancing immunosuppressive therapy with prolonged antimicrobial treatment is challenging and likely to become more common as the number of individuals being treated with biologics and immunosuppressive agents increases.
Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , Bronchiectasis/complications , Microscopic Polyangiitis/diagnosis , Mycobacterium Infections, Nontuberculous/complications , Mycobacterium abscessus/isolation & purification , Aged , Anti-Bacterial Agents/therapeutic use , Female , Humans , Mycobacterium Infections, Nontuberculous/drug therapyABSTRACT
The incidence of non-tuberculous mycobacteria (NTM) infection is increasing in Europe. However, a picture of Italian epidemiology and clinical practice is missing. We performed a national Italian survey involving 42 respiratory medicine departments. The NTM species more frequently isolated were Mycobacterium avium complex, followed by M. xenopi and M. kansasii. Patients with NTM were more frequently female (57%), and over 60 years of age, with bronchiectasis and COPD as main comorbidities. Bronchoscopic samples were widely used in the diagnostic phase. Of all patients with NTM, 73% met the criteria for NTM pulmonary disease. Despite strong adherence to the guidelines, physicians found significant difficulties related to pharmacological adverse events, patients' compliance and poor outcomes. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 21-25).