Clinical significance of fractional exhaled nitric oxide and periostin as potential markers to assess therapeutic efficacy in patients with cough variant asthma

BackgroundIn Japan, cough variant asthma (CVA) is the most common etiology of chronic cough. Contrary to substantial progress in understanding the roles of various factors in classic asthma, little is known regarding the pathogenesis and development of CVA. Furthermore, few studies have explored valuable biomarkers for evaluating the therapeutic efficacy of patients with CVA.MethodsWe conducted a single-center, prospective study to investigate the clinical significance of various clinical factors as potential “therapeutic” markers for CVA.ResultsFrom December 2019 to September 2020, we enrolled 20 patients with CVA and 10 age-matched healthy control subjects. Fractional exhaled nitric oxide (FeNO) values were significantly higher in patients with CVA than those in healthy controls. All patients with CVA commenced treatment at the initial visit, which markedly alleviated symptoms 12 weeks after treatment. FeNO values and serum periostin levels were significantly decreased following treatment, and altered FeNO values correlated with improved visual analogue scale scores of symptoms. Moreover, changes in both FeNO values and serum periostin levels were significantly correlated with increased values of some pulmonary function tests while also correlating with each other.ConclusionsOur observations indicate the usefulness of FeNO and periostin as potential “therapeutic” markers for CVA. To the best of our knowledge, this is the first report demonstrating the clinical significance of these factors as potential biomarkers to assess therapeutic efficacy in patients with CVA.     

Role of serum periostin in the management of asthma and its comorbidities

Type-2 airway inflammation is a major characteristic of asthma. Assessing its degree of severity is, therefore, essential in asthma management. Periostin, a matricellular protein belonging to the fasciclin family, is a key molecule linking type-2 airway inflammation and airway remodeling. Fortunately, periostin can be detected in the blood and used to provide sustaining airway information on type-2 inflammation and remodeling. Serum periostin is elevated in the eosinophilic/type 2 subtype of severe asthma, and its levels remain relatively stable and reflect genetic backgrounds. This suggests that serum periostin may serve as a marker of geno-endophenotype with type-2 airway inflammation and thus could be a predictive marker of the long-term prognosis of asthma under treatment. As expected, serum periostin is particularly elevated in comorbidities associated with the eosinophilic/type 2 subtype of severe asthma, including eosinophilic chronic rhinosinusitis, aspirin-exacerbated respiratory diseases, allergic bronchopulmonary aspergillosis, and eosinophilic granulomatosis with polyangiitis. Conversely, serum periostin levels are relatively lower in the overweight/obese. Serum periostin measurements may help to significantly improve the management of patients with severe asthma.     

Lung function decline in sarcoidosis

BackgroundA decline in lung function is the basis of the definition of progressive fibrosing interstitial lung disease. This study aimed to evaluate the epidemiology and clinical relevance of lung function decline in sarcoidosis.MethodsThis retrospective observational study was conducted at a general sarcoidosis clinic. Lung function decline was defined as a relative 24-month decline in the percentage of predicted forced vital capacity (%FVC) of ≥10% or the percentage of predicted diffusion capacity for carbon monoxide (%DLco) of ≥15%. The frequency of lung function decline and its associations with the subsequent 24-month change in lung function and survival time were analyzed.ResultsOf the 201 patients, 14 (7.0%) exhibited a 24-month decline in %FVC of ≥10% and 28 (16.6%) exhibited a 24-month decline in %DLco of ≥15%. A 24-month decline in lung function was not associated with a subsequent 24-month lung function decline. Eleven patients died during the median observational time of 148.3 months; 4 of the 11 deaths were associated with sarcoidosis. A 24-month decline in lung function was associated with worse survival even after the adjustment for composite physiological index (CPI) and pulmonary hypertension (PH): 24-month decline in %FVC ≥10%, hazard ratio (HR) adjusted for CPI = 21.8, HR adjusted for PH = 19.3 and 24-month decline in %DLco ≥15%, HR adjusted for PH = 6.74.ConclusionsA 24-month decline in lung function can be a risk factor for mortality in sarcoidosis irrespective of CPI and PH.     

Hydrogen sulfide as a novel biomarker of asthma and chronic obstructive pulmonary disease

Hydrogen sulfide (H₂S) has recently been recognised as the third important gas-signalling molecule, besides nitric oxide and carbon monoxide. H₂S has been reported to be produced by many cell types in mammalian tissues and organs throughout the actions of H₂S-generating enzymes or redox reactions between the oxidation of glucose and element of sulfur. Although the pathological role of H₂S has not yet been fully elucidated, accumulative data suggest that H₂S may have biphasic effects. Briefly, it mainly has anti-inflammatory and antioxidant roles, although it can also have pro-inflammatory effects under certain conditions where rapid release of H₂S in tissues occur, such as sepsis. To date, there have been several clinical studies published on H₂S in respiratory disorders, including asthma and chronic obstructive pulmonary disease (COPD). According to previous studies, H₂S is detectable in serum, sputum, and exhaled breath, although a gold standard method for detection has not yet been established. In asthma and COPD, H₂S levels in serum and sputum can vary depending on the underlying conditions such as an acute exacerbation. Furthermore, sputum H₂S in particular correlates with sputum neutrophils and the degree of airflow limitation, indicating that H₂S has potential as a novel promising biomarker for neutrophilic airway inflammation for predicting current control state as well as future risks of asthma. In the future, concurrent measures of H₂S with conventional inflammatory biomarkers (fractional exhaled nitric oxide, eosinophils etc) may provide more useful information regarding the identification of inflammatory phenotypes of asthma and COPD for personalised treatment.     

Basal interventricular septum thinning and long-term left ventricular function in patients with sarcoidosis

BackgroundBasal interventricular septum (IVS) thinning on transthoracic echocardiography (TTE) is highly specific to cardiac sarcoidosis. Although basal IVS thinning is listed as one of the five major diagnostic criteria for cardiac sarcoidosis, its association with long-term cardiac function has not been investigated. This study aimed to evaluate the epidemiology and clinical relevance of basal IVS thinning in a clinic-based cohort of patients with sarcoidosis.MethodsThis retrospective observational study was conducted at a general sarcoidosis clinic. The incidence of basal IVS thinning and associations with variables at baseline and a delayed onset of left ventricular (LV) dysfunction (LV ejection fraction [LVEF] < 50%) were analyzed.ResultsOf the 1009 patients, 23 (2.3%) had basal IVS thinning. Basal IVS thinning was associated with cardiac pacemaker (PM) implantation at baseline (adjusted odds ratio = 20.5; 95% confidence interval [CI] = 7.9–53.2; P < 0.01). Of the 768 patients with an LVEF of ≥50% at baseline who underwent one or more longitudinal TTEs after baseline, 36 (4.7%) developed LV dysfunction over a median observation period of 88.9 months. Basal IVS thinning and PM implantation at baseline were the independent predictors of a delayed onset of LV dysfunction (basal IVS thinning, adjusted hazard ratio [HR] = 3.7; 95% CI = 1.5–9.6; PM implantation, adjusted HR = 15.7; 95% CI = 7.4–33.3).ConclusionsBasal IVS thinning in patients with sarcoidosis can predict a delayed onset of LV dysfunction even when the LV function is preserved at the time of detection.     

[18F]-Florbetaben PET/CT for Differential Diagnosis Among Cardiac Immunoglobulin Light Chain,Transthyretin Amyloidosis,and Mimicking Conditions

ObjectivesThis study aimed to test the diagnostic value of [18F]–florbetaben positron emission tomography (PET) in patients with suspicion of CA.BackgroundDiagnosis of cardiac involvement in immunoglobulin light-chain–derived amyloidosis (AL) and transthyretin-related amyloidosis (ATTR), which holds major importance in risk stratification and decision making, is frequently delayed. Furthermore, although diphosphonate radiotracers allow a noninvasive diagnosis of ATTR, demonstration of cardiac amyloidosis (CA) in AL may require endomyocardial biopsy.MethodsForty patients with biopsy-proven diagnoses of CA (20 ALs, 20 ATTRs) and 20 patients referred with the initial clinical suspicion and later diagnosed with non-CA pathology underwent a cardiac PET/computed tomography scan with a 60-min dynamic [18F]-florbetaben PET acquisition, and 4 10-min static scans at 5, 30, 50, and 110 min after radiotracer injection.ResultsVisual qualitative assessment showed intense early cardiac uptake in all subsets. Patients with AL displayed a high, persistent cardiac uptake in all the static scans, whereas patients with ATTR and those with non-CA showed an uptake decrease soon after the early scan. Semiquantitative assessment demonstrated higher mean standardized uptake value (SUV_mean) in patients with AL, sustained over the whole acquisition period (early SUV_mean: 5.55; interquartile range [IQR]: 4.00 to 7.43; vs. delayed SUV_mean: 3.50; IQR: 2.32 to 6.10; p = NS) compared with in patients with ATTR (early SUV_mean: 2.55; IQR: 1.80 to 2.97; vs. delayed SUV_mean: 1.25; IQR: 0.90 to 1.60; p < 0.001) and in patients with non-CA (early SUV_mean: 3.50; IQR: 1.60 to 3.37; vs. delayed SUV_mean: 1.40; IQR: 1.20 to 1.60; p < 0.001). Similar results were found comparing heart-to-background ratio and molecular volume.ConclusionsDelayed [18F]-florbetaben cardiac uptake may discriminate CA due to AL from either ATTR or other mimicking conditions. [18F]-florbetaben PET/computed tomography may represent a promising noninvasive tool for the diagnosis of AL amyloidosis, which is still often challenging and delayed. (A Prospective Triple-Arm, Monocentric, Phase-II Explorative Study on Evaluation of Diagnostic Efficacy of the PET Tracer [18F]-Florbetaben [Neuraceq] in Patients With Cardiac Amyloidosis [FLORAMICAR2]; EudraCT number: 2017-001660-38)     

Prevalence of pulmonary embolism in patients with obstructive sleep apnea and chronic obstructive pulmonary disease: The overlap syndrome

ObjectiveGrowing evidence indicates that both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may be closely associated with the prevalence of pulmonary embolism (PE). However, the relationship of overlap syndrome (OS) (coexistence of OSA and COPD) with PE is unclear. The purpose of this study was to investigate whether OS were associated with increased PE prevalence.MethodsWe performed a retrospective chart review of patients who underwent sleep study at Beijing An Zhen Hospital from 2011 to 2014. The association of OS with PE prevalence was estimated by using logistic regression models.ResultsIn contrast to control patients (neither OSA nor COPD), those subjects with OS had higher odds of PE (OR9.61; 95%CI 4.02–21.31, p < 0.001) with significance persisting after adjusting for covariates (OR 5.66; 95%CI 1.80–16.18, p = 0.004). Meanwhile, patients with OS compared with those with isolated OSA also had significantly higher odds of PE in univariate (OR 4.79; 95%CI 2.04–10.33, p = 0.0007) and adjusted models (OR 3.89; 95%CI 1.27–10.68, p = 0.019). In subgroup analysis, patients with OS had higher odds of PE than control group among male subjects (OR 8.12, 95%CI1.86–31.87, p = 0.007) and patients ≥ 58years (OR 5.50, 95%CI 1.51–18.14, p = 0.012) in multivariable models. Percentage of total sleep time with saturation lower than 90% (T90) ≥ 2.6% was significantly associated with prevalence of PE (OR 4.72, 95%CI1.34–19.83, p = 0.015) in subgroup of patients older than 58.ConclusionsOS is independently associated with PE prevalence. Longitudinal studies are needed to better understand the relationship with incident PE.     

Bronchoscopy for the diagnosis of nontuberculous mycobacterial pulmonary disease: Specificity and diagnostic yield in a retrospective cohort study

BackgroundBronchoscopy is a recognized method for obtaining specimens for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnostic properties remain to be elucidated. The aim of this study was to determine the specificity of bronchoscopy for the diagnosis of NTM-PD, and to examine the diagnostic yield of bronchoscopy for detecting nontuberculous mycobacteria (NTM) when patients cannot expectorate sputum with NTM.MethodsThis retrospective cohort study included 2657 patients who underwent bronchoscopy and mycobacterial culture between January 2004 and June 2018 in a tertiary care center in Tokyo, Japan. To examine the specificity of bronchoscopy, the first cohort comprised patients who underwent bronchoscopy for the diagnosis of lung cancer and mycobacterial culture. To investigate the diagnostic yield, patients with nodular bronchiectasis who underwent bronchoscopy for the diagnosis of NTM-PD were enrolled into the second cohort.ResultsIn total, 919 patients were diagnosed with lung cancer, 19 patients showed positive culture for NTM, and 14 patients showed findings for NTM-PD. Accordingly, the specificity was calculated as 900/905 (99.4%). In addition, NTM-PD was suspected before bronchoscopy in 199 patients; the diagnostic yield was 105/199 (52.8%). Four factors were associated with NTM-PD: upper lobe examination, absence of specific bacteria, absence of connective tissue disease, and a higher total computed tomography score.ConclusionsBronchoscopy has a high specificity for the diagnosis of NTM-PD. In addition, even when NTM is undetected in sputum, bronchoscopy may detect mycobacteria in approximately half of the patients suspected of having NTM-PD.     

Plasma phospholipid dysregulation in patients with cystathionine-β synthase deficiency

Background & aimsPatients with cystathionine β-synthase deficiency (CBSD) exhibit high circulating levels of homocysteine and enhanced lipid peroxidation. We have characterized the plasma lipidome in CBSD patients and related lipid abnormalities with reactions underlying enhanced homocysteine levels.Methods and resultsUsing an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, plasma lipids were determined with an untargeted lipidomics approach in 11 CBSD patients and 11 matched healthy subjects (CTRL). Compared to CTRL, CBSD patients had a higher medium and long-chain polyunsaturated fatty acids (PUFA) content in phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) species (p < 0.02), and depletion of phosphatidylcholine (PC; p = 0.02) and of lysophosphatidylcholine (LPC; p = 0.003) species containing docosahexaenoic acid (DHA), suggesting impaired phosphatidylethanolamine-N-methyltransferase (PEMT) activity. PEMT converts PE into PC using methyl group by S-adenosylmethionine (SAM) thus converted in S-adenosylhomocysteine (SAH). Whole blood SAM and SAH concentrations by liquid chromatography tandem mass spectrometry were 1.4-fold (p = 0.015) and 5.3-fold (p = 0.003) higher in CBSD patients than in CTRL. A positive correlation between SAM/SAH and PC/PE ratios (r = 0.520; p = 0.019) was found.ConclusionsA novel biochemical abnormality in CBSD patients consisting in depletion of PC and LPC species containing DHA and accumulation of PUFA in PE and LPE species is revealed by this lipidomic approach. Changes in plasma SAM and SAH concentrations are associated with such phospholipid dysregulation. Given the key role of DHA in thrombosis prevention, depletion of PC species containing DHA in CBSD patients provides a new direction to understand the poor cardiovascular outcome of patients with homocystinuria.     

Clinical characteristics,outcomes, and factors associated with mortality in Nocardia pneumonia: 18 years' real-world data from a tertiary care hospital in Karachi,Pakistan

BackgroundPulmonary nocardiosis is a rare pulmonary infection with high morbidity and mortality. Limited real-world data on pulmonary nocardiosis patients are available from developing countries like Pakistan.MethodsThis retrospective observational study was conducted at the Aga Khan University Hospital, Karachi, Pakistan, from August 2003 to June 2020. Demographics, immune status, underlying diseases, laboratory data, treatment, and outcomes of all nocardiosis patients were recorded in predesigned proforma.ResultsSixty-six patients with smear/culture-proven pulmonary nocardiosis were identified. Most patients (83.3%) were treated with trimethoprim-sulfamethoxazole alone or in combination with other medicines. The overall mortality rate in our study was 33.3% (n = 22/66). Factors significantly associated with mortality were respiratory failure (p < 0.001), raised procalcitonin levels (p = 0.01), concomitant fungal infections (p = 0.01), concomitant TB (p = 0.03), and patients on combination therapy (p < 0.001).Respiratory failure (odds ratio [OR] 46.94 [95% confidence intervals [CI]: 5.01–439.03] p < 0.001), concomitant fungal infection (OR 17.09 [95% CI: 1.47–197.88] p- = 0.02) and patients on combination therapy (OR 6.90 [95% CI: 1.23–38.61] p = 0.02) were also identified as independent risk factors for mortality on multivariate analysis.ConclusionsThis study provides essential information on the clinical characteristics and risk factors, outcomes, and factors associated with mortality for pulmonary nocardial infections.     

Lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for Mycobacterium avium complex pulmonary disease

BackgroundEthambutol ocular toxicity is a major problem during combination chemotherapy for Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD) due to years-long therapy for MAC.ObjectivesThis study aimed to identify the lower dose of daily ethambutol that can reduce ocular toxicity.MethodsWe retrospectively reviewed the medical records of 312 patients who visited The University of Tokyo Hospital between January 2007 and December 2017 for nontuberculous mycobacterial pulmonary disease. Seventy-six patients with MAC-PD who were treated with combination chemotherapy for the first time were analyzed in this study.ResultsEthambutol was discontinued because of visual symptoms in 13 patients (17%), 7 of whom were diagnosed with ethambutol ocular neuropathy. The dose per body weight was significantly higher in patients who developed ocular neuropathy than in those who did not (15.4 mg/kg/d vs. 12.5 mg/kg/d, respectively; p = 0.048). We assigned patients to higher or lower dose groups according to the median dose of 12.5 mg/kg/d. Although ocular neuropathy developed in 6 out of 38 patients in the higher dose group, ocular neuropathy developed in 1 out of 38 patients in the lower dose group (16% vs. 3%, respectively; p = 0.038). The failures of sputum culture conversion and radiological improvement were not significantly different between the two groups (p = 0.638 and 0.305, respectively). Macrolide resistance developed in one patient per group during follow-up (3% per group, p = 0.945).ConclusionsA lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for pulmonary MAC infection.     

High prevalence of airway obstruction and pulmonary emphysema in urothelial (renal pelvis,ureter, and bladder) cancer patients

BackgroundCigarette smoking is a major cause of COPD, with patients also presenting complications that stem from other smoking-related diseases, including urothelial cancer. However, the prevalence of COPD or airflow obstruction in urothelial cancer patients has not been well studied.MethodsWe investigated the prevalence of airflow obstruction (FEV1/FVC < 70%) in newly diagnosed urothelial cancer patients and identified the risk factors for airflow obstruction in existing urothelial cancer patients. Additionally, we compared the characteristics of subjects who had been diagnosed with both airflow obstruction and urothelial cancer, and subjects whose airflow obstruction was discovered during health screenings.ResultsA total of 217 patients were newly diagnosed with urothelial cancer during the study period at our institution. Among all patients, 210 (96.8%) underwent an evaluable lung function test, in which 38.6% (81 patients) displayed airflow obstruction defined as FEV1/FVC < 70%. In urothelial cancer patients, age, smoking index (pack-years), and BMI proved to be significant risk factors for airflow obstruction in multivariate logistic regression (p = 0.007, p < 0.0001, and p = 0.035, respectively). Gender, cancer stage, and cancer location were not significant risk factors. Patients with both airflow obstruction and urothelial cancer showed a more advanced emphysematous change than subjects presenting with airflow obstruction alone (unpaired t-test, p = 0.0003).ConclusionsAirflow obstruction was identified in 38.6% of urothelial cancer patients. Age, smoking index (pack-years), and BMI were significant risk factors. A significantly higher emphysematous score was observed in subjects with urothelial cancer than in subjects with airway obstruction alone.     

Idiopathic pulmonary fibrosis: Molecular mechanisms and potential treatment approaches

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease with high mortality that commonly occurs in middle-aged and older adults. IPF, characterized by a decline in lung function, often manifests as exertional dyspnea and cough. Symptoms result from a fibrotic process driven by alveolar epithelial cells that leads to increased migration, proliferation, and differentiation of lung fibroblasts. Ultimately, the differentiation of fibroblasts into myofibroblasts, which synthesize excessive amounts of extracellular matrix proteins, destroys the lung architecture. However, the factors that induce the fibrotic process are unclear. Diagnosis can be a difficult process; the gold standard for diagnosis is the multidisciplinary conference. Practical biomarkers are needed to improve diagnostic and prognostic accuracy. High-resolution computed tomography typically shows interstitial pneumonia with basal and peripheral honeycombing. Gas exchange and diffusion capacity are impaired. Treatments are limited, although the anti-fibrotic drugs pirfenidone and nintedanib can slow the progression of the disease. Lung transplantation is often contraindicated because of age and comorbidities, but it improves survival when successful. The incidence and prevalence of IPF has been increasing and there is an urgent need for improved therapies. This review covers the detailed cellular and molecular mechanisms underlying IPF progression as well as current treatments and cutting-edge research into new therapeutic targets.     

Chondroitin sulfate in tissue remodeling: Therapeutic implications for pulmonary fibrosis

Fibrosis is characterized by the deposition of extracellular matrix (ECM) proteins, while idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease characterized by dysregulated tissue repair and remodeling. Anti-inflammatory drugs, such as corticosteroids and immunosuppressants, and antifibrotic drugs, like pirfenidone and nintedanib, are used in IPF therapy. However, their limited effects suggest that single mediators are inadequate to control IPF. Therefore, therapies targeting the multifactorial cascades that regulate tissue remodeling in fibrosis could provide alternate solutions. ECM molecules have been shown to modulate various biological functions beyond tissue structure support and thus, could be developed into novel therapeutic targets for modulating tissue remodeling. Among ECM molecules, glycosaminoglycans (GAG) are linear polysaccharides consisting of repeated disaccharides, which regulate cell-matrix interactions. Chondroitin sulfate (CS), one of the major GAGs, binds to multifactorial mediators in the ECM and reportedly participates in tissue remodeling in various diseases; however, to date, its biological functions have drawn considerably less attention than other GAGs, like heparan sulfate. In the present review, we discuss the involvement and regulation of CS in tissue remodeling and pulmonary fibrotic diseases, its role in pulmonary fibrosis, and the therapeutic approaches targeting CS.     

Asbestos exposure and tuberculous pleurisy as developmental causes of progressive unilateral upper-lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis

BackgroundUnilateral upper-lung field pulmonary fibrosis (upper-PF), which is radiologically consistent with pleuroparenchymal fibroelastosis, develops after thoracic surgery. In most patients with unilateral upper-PF, aberrant intra-/extra thoracic air commonly emerges and an autopsy shows chronic pleuritis, which indicates that pleural involvement is associated with upper-PF development. If so, there may be patients with unilateral upper-PF who have a history of pleural involvement, including tuberculous pleurisy (TP) or asbestos exposure (AE). This study aimed to examine this supposition.MethodsWe examined the radiological reports of all consecutive patients from 2012 to 2018 to investigate whether there were patients having unilateral upper-PF and a history of TP or AE.ResultsEight patients were included in the study. Five patients had a history of TP, and the remaining three had that of AE. All patients were men and had respiratory symptoms, and seven patients presented with restrictive ventilatory impairment. The interval between TP or last AE and upper-PF development was long, with a median of over 20 years. The upper-PF lesion was commonly located in the right lung, and aberrant intrathoracic air was observed in five patients during their clinical course. Additionally, the upper-PF lesion transformed into a cystic lesion in six patients, which resulted in Aspergillus infection in two patients. The prognosis was poor, with a median overall survival of 38 months.ConclusionsUnilateral upper-PF developed even in patients with a history of pleural involvement. Our results indicate that pleural involvement plays an important role in the development of unilateral upper-PF.     

Treatment strategies with alternative treatment options for patients with Mycobacterium avium complex pulmonary disease

Diseases caused by Mycobacterium avium complex (MAC) infection in the lungs are increasing worldwide. The recurrence rate of MAC-pulmonary disease (PD) has been reported to be as high as 25–45%. A significant percentage of recurrences occurs because of reinfection with a new genotype from the environment. A focus on reducing exposure to MAC organisms from the environment is therefore an essential component of the management of this disease as well as standard MAC-PD treatment. A macrolide-containing three-drug regimen is recommended over a two-drug regimen as a standard treatment, and azithromycin is recommended rather than clarithromycin. Both the 2007 and 2020 guidelines recommend a treatment duration of MAC-PD of at least one year after the culture conversion. Previous clinical studies have reported that ethambutol could prevent macrolide resistance. Furthermore, the concomitant use of aminoglycoside, amikacin liposomal inhalation, clofazimine, linezolid, bedaquiline, and fluoroquinolone with modification of guideline-based therapy has been studied.Long-term management of MAC-PD remains challenging because of the discontinuation of multi-drug regimens and the acquisition of macrolide resistance. Moreover, the poor compliance of guideline-based therapy for MAC-PD treatment worldwide is concerning since it causes macrolide resistance.Therefore, in this review, we focus on MAC-PD treatment and summarize various treatment options when standard treatment cannot be maintained, with reference to the latest ATS/ERS/ESCMID/IDSA clinical practice guidelines revised in 2020.     

Rare,Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists

Recurrent abdominal pain is a common reason for repeated visits to outpatient clinics and emergency departments, reflecting a substantial unmet need for timely and accurate diagnosis. A lack of awareness of some of the rarer causes of recurrent abdominal pain may impede diagnosis and delay effective management. This article identifies some of the key rare but diagnosable causes that are frequently missed by gastroenterologists and provides expert recommendations to support recognition, diagnosis, and management with the ultimate aim of improving patient outcomes.