A Puerto Rican Variant of Lady Windermere Syndrome: Reanalyzing the Characteristics of Non-tuberculous Mycobacterial Infection.

Lady Windermere syndrome (LWS) is a disease caused by a non-tuberculous Mycobacterium (NTM) that is commonly found in thin women who voluntarily suppress their cough reflex. The NTM that causes this syndrome is Mycobacterium avium complex, an organism commonly present in chlorinated city water and soil. Patients with LWS are tall, lean, elderly white women. We report a case of an immunocompetent 81-year-old thin Puerto Rican female with a recurrent cough since childhood, who was misdiagnosed with tuberculosis (TB) and prophylactically treated. While the patient fitted the clinical picture of NTM pulmonary infection based on symptoms, imaging, and microbiologic findings, her demography and morphologic features were not completely consistent with published findings. The incidence and prevalence of NTM lung disease are rising worldwide due to the aging population, increased use of immunosuppressive medications, and prevalence of chronic pulmonary obstructive disease and bronchiectasis. The goal of this report is to increase awareness of LWS as one of the diagnoses that should be considered in patients presenting with clinical findings resembling TB and bring attention to the different clinical characteristics this patient with LWS possessed.

Lady Windermere Syndrome: A Rare Differential Diagnosis for Hemoptysis.

Mycobacterium avium complex (MAC) is often observed in immunocompromised individuals. However, when pulmonary MAC infection occurs in immunocompetent individuals, particularly elderly females, characteristically involving the middle lobe and lingula lobe of the lung, it is known as Lady Windermere syndrome (LWS). A 64-year-old female patient with no significant comorbidities presented with a history of low-grade intermittent fever and dry cough for one-month duration complicated with hemoptysis for two days. Her initial investigations and imaging were negative, except for the high-resolution CT (HRCT) finding of bronchiectasis involving the middle lobe and lingula lobe suggestive of MAC infection, which was further confirmed by positive sputum culture for MAC. LWS is a condition that is rarely encountered in clinical settings and seldom described in the literature. Especially in resource-limited settings, arriving at a diagnosis is further hindered by the scarce availability of advanced imaging such as HRCT. In clinical settings where pulmonary tuberculosis is endemic, the differentiation of the two conditions is of paramount importance as the treatment regimens for the two conditions are quite different.

Nontuberculous Mycobacteria, Mucociliary Clearance, and Bronchiectasis.

Nontuberculous mycobacteria (NTM) are environmental and ubiquitous, but only a few species are associated with disease, often presented as nodular/bronchiectatic or cavitary pulmonary forms. Bronchiectasis, airways dilatations characterized by chronic productive cough, is the main presentation of NTM pulmonary disease. The current Cole's vicious circle model for bronchiectasis proposes that it progresses from a damaging insult, such as pneumonia, that affects the respiratory epithelium and compromises mucociliary clearance mechanisms, allowing microorganisms to colonize the airways. An important bronchiectasis risk factor is primary ciliary dyskinesia, but other ciliopathies, such as those associated with connective tissue diseases, also seem to facilitate bronchiectasis, as may occur in Lady Windermere syndrome, caused by M. avium infection. Inhaled NTM may become part of the lung microbiome. If the dose is too large, they may grow excessively as a biofilm and lead to disease. The incidence of NTM pulmonary disease has increased in the last two decades, which may have influenced the parallel increase in bronchiectasis incidence. We propose that ciliary dyskinesia is the main promoter of bronchiectasis, and that the bacteria most frequently involved are NTM. Restoration of ciliary function and impairment of mycobacterial biofilm formation may provide effective therapeutic alternatives to antibiotics.

Lady Windermere Syndrome: Unravelling an Older Lady's Nightmare.

Infection with nontuberculous mycobacteria (NTM) is an increasingly important cause of pulmonary disease, particularly in immunocompromised patients or those suffering from chronic lung conditions. However, though rare, non-tubercular mycobacterial infection and bronchiectasis may also occur in an immunocompetent patient. This unusual condition is typically seen in middle-aged or elderly white females, with bronchiectasis having a predilection for the middle lobe and lingula. Here, we present a similar case of Mycobacterium avium complex (MAC) infection with middle lobe bronchiectasis in an elderly immunocompetent female, recognized as Lady Windermere Syndrome (LWS).

Infección pulmonar por micobacterias no tuberculosas / Lung infection with nontuberculous mycobacteria

Objetivo: Describir la epidemiología y hallazgos en tomografía computarizada (TC) de las infecciones pulmonares por micobacterias no tuberculosas (IPMNT) y su evolución según el tratamiento. Material y métodos: Estudio retrospectivo de 131 pacientes consecutivos con cultivos positivos para micobacterias no tuberculosas (MNT) entre 2005 y 2016. Se seleccionaron los que cumplían con los criterios diagnósticos de IPMNT. Se analizaron los datos epidemiológicos, clínicos, microbiológicos, radiológicos, el tratamiento recibido y la evolución en función de este. Resultados: Se incluyeron 34 pacientes con una edad media de 55 años, el 67,6% hombres. El 50% estaba inmunodeprimido (VIH positivos, el 58,8%); el 20,6% tenía EPOC; el 5,9%, neoplasias conocidas; el 5,9%, fibrosis quística; y el 29,4% no presentaba comorbilidades. El 20,6% presentaba antecedentes de tuberculosis y el 20,6% estaba infectado por otros microorganismos. Mycobacterium avium complex fue el germen más frecuentemente aislado (52,9%). Siete pacientes (20,6%) presentaron además infecciones por otros microorganismos. En la TC, los hallazgos más frecuentes fueron: nódulos (64,7%), patrón en árbol en brote (61,8%), nódulos centrolobulillares (44,1%), consolidaciones (41,2%), bronquiectasias (35,3%) y cavidades (32,4%). Se realizó un estudio comparativo de los hallazgos entre hombres y mujeres y entre pacientes inmunodeprimidos e inmunocompetentes. El 67,6% recibió antituberculostáticos (el 72% mostró mejoría) y el 20,6%, antibióticos convencionales (todos con mejoría radiológica). Conclusión: El diagnóstico de la IPMNT es complejo. Los hallazgos clínicos y radiológicos son inespecíficos y un porcentaje importante de pacientes puede presentar otras infecciones concomitantes.(AU)

Objective: To describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment. Material and methods: We retrospectively studied 131 consecutive patients with positive cultures for nontuberculous mycobacteria between 2005 and 2016. We selected those who met the criteria for nontuberculous mycobacterial lung infection. We analyzed the epidemiologic data; clinical, microbiological, and radiological findings; treatment; and outcome according to treatment. Results: We included 34 patients (mean age, 55 y; 67.6% men); 50% were immunodepressed (58.8% of these were HIV+), 20.6% had COPD, 5.9% had known tumors, 5.9% had cystic fibrosis, and 29.4% had no comorbidities. We found that 20.6% had a history of tuberculosis and 20.6% were also infected with other microorganisms. Mycobacterium avium complex was the most frequently isolated germ (52.9%); 7 (20.6%) were also infected with other organisms. The most common CT findings were nodules (64.7%), tree-in-bud pattern (61.8%), centrilobular nodules (44.1%), consolidations (41.2%), bronchiectasis (35.3%), and cavities (32.4%). We compared findings between men and women and between immunodepressed and immunocompetent patients. Treatment was antituberculosis drugs in 67.6% of patients (72% of whom showed improvement) and conventional antibiotics in 20.6% (all of whom showed radiologic improvement). Conclusion: The diagnosis of nontuberculous mycobacterial lung infections is complex. The clinical and radiologic findings are nonspecific and a significant percentage of pateints can have other, concomitant infections.(AU)

Lung infection with nontuberculous mycobacteria.

OBJECTIVE: To describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment. MATERIAL AND METHODS: We retrospectively studied 131 consecutive patients with positive cultures for nontuberculous mycobacteria between 2005 and 2016. We selected those who met the criteria for nontuberculous mycobacterial lung infection. We analysed the epidemiologic data; clinical, microbiological, and radiological findings; treatment; and outcome according to treatment. RESULTS: We included 34 patients (mean age, 55 y; 67.6% men); 50% were immunodepressed (58.8% of these were HIV+), 20.6% had COPD, 5.9% had known tumors, 5.9% had cystic fibrosis, and 29.4% had no comorbidities. We found that 20.6% had a history of tuberculosis and 20.6% were also infected with other microorganisms. Mycobacterium avium complex was the most frequently isolated germ (52.9%); 7 (20.6%) were also infected with other organisms. The most common CT findings were nodules (64.7%), tree-in-bud pattern (61.8%), centrilobular nodules (44.1 %), consolidations (41.2%), bronchiectasis (35.3%), and cavities (32.4%). We compared findings between men and women and between immunodepressed and immunocompetent patients. Treatment was antituberculosis drugs in 67.6% of patients (72% of whom showed improvement) and conventional antibiotics in 20.6% (all of whom showed radiologic improvement). CONCLUSION: The diagnosis of nontuberculous mycobacterial lung infections is complex. The clinical and radiologic findings are nonspecific and a significant percentage of pateints can have other, concomitant infections.

Osteoporosis in nontuberculous mycobacterial pulmonary disease: a cross-sectional study.

BACKGROUND: Since nontuberculous mycobacterial pulmonary disease (NTM-PD) is common in middle-aged/elderly slender women at risk of osteoporosis, we hypothesized that NTM-PD could be associated with osteoporosis. The study aimed to evaluate the prevalence of osteoporosis in patients with NTM-PD compared with that in the general population and determine the factors associated with osteoporosis in the subjects, including the serum estradiol (E2) and 25-hydroxyvitamin D (25OHD) levels. METHODS: We have recruited 228 consecutive adult patients with NTM-PD from a prospective cohort study at the Keio University Hospital, who had no history of osteoporosis or osteoporosis-associated bone fracture but underwent dual-energy X-ray absorptiometry-based bone mineral density (BMD) evaluation from August 2017-September 2019. The E2 and 25OHD levels were measured in 165 patients with available stored serum samples. We performed multivariable logistic regression analyses for osteopenia and osteoporosis. RESULTS: Osteoporosis (T-score ≤ - 2.5) and osteopenia (T-score - 1 to - 2.5) were diagnosed in 35.1% and 36.8% of patients with NTM-PD, respectively. Compared with the general population, the proportion of osteoporosis was significantly higher in 50-59-, 60-69-, and 70-79-year-old women with NTM-PD. Multivariable analysis revealed that older age (adjusted odds ratio [aOR] for 1-year increase = 1.12; 95% confidence interval [CI] = 1.07-1.18), female sex (aOR = 36.3; 95% CI = 7.57-174), lower BMI (aOR for 1 kg/m2 decrease = 1.37; 95% CI = 1.14-1.65), and chronic Pseudomonas aeruginosa (PA) infection (aOR = 6.70; 95% CI = 1.07-41.8) were independently associated with osteoporosis. Additionally, multivariable analysis in 165 patients whose serum E2 and 25OHD levels were measured showed that both low E2 levels (< 10 pg/mL) and lower 25OHD levels were independently associated with osteoporosis. CONCLUSIONS: Middle-aged/elderly women with NTM-PD have a higher prevalence of osteoporosis than the general population. BMD screening should be considered in NTM-PD, especially in older females with severe diseases such as chronic PA infection and lower BMI, and low serum E2 and 25OHD levels.

In Defense of Lady Windermere Syndrome.

Defense of Lady Windermere Syndrome (LWS) provides a critical analysis of its proposed pathogenesis, evidence supporting a causal role of volitional cough suppression, pathogenesis of M. avium complex (MAC) superimposition, a defense of the eponym, and cites a possible contribution of LWS to the bronchiectasis population.

Lady Windermere syndrome in Castile and León. / Síndrome de Lady Windermere en Castilla y León.

INTRODUCTION: Lady Windermere syndrome (LWS) is a pulmonary disease caused by Mycobacterium avium complex (MAC). The objective of this study is to ascertain its frequency and characteristics in the northern area of the autonomous community of Castile and León. METHODS: A retrospective study of patients with MAC isolates in respiratory samples from five public hospitals in the autonomous community over a six-year period, following the ATS/IDSA criteria. The MAC strains were identified by GenoType Mycobacterium reverse hybridisation probes or PCR-RFLP analysis of the hsp65 gene. RESULTS: Of 183 cases of MAC identified, only five women (2.7%) aged 68.8±10.7years met LWS criteria. In three cases, MAC was isolated jointly and intermittently with other pathogens. Only one patient was treated according to ATS/IDSA criteria. DISCUSSION: LWS remains underestimated, with affected patients representing a significant burden on healthcare resources over long periods of time. As a result, greater microbiological and therapeutic knowledge of the syndrome is needed.

Síndrome de Lady Windermere como causa de tos crónica. A propósito de un caso / Lady Windermere Syndrome as a cause of chronic cough. Report of a case

Resumen Las mycobacterias no tuberculosas son poco reconocidas en la actualidad, pero su prevalencia se incrementa al sospechar su presencia en inmunodeprimidos o en enfermedades crónicas como la fibrosis quística. Se presenta el caso de una paciente con diagnóstico de síndrome de Lady Windermere con tos crónica. Se realizó tomografía computarizada donde se observaron bronquiectasias en el segmento lingular del pulmón izquierdo y en los lóbulos medio e inferior del derecho. En la broncoscopia se aisló complejo Mycobacterium avium-intracellulare. El no considerar en el diagnóstico de pacientes con tos crónica y sin factores predisponentes a las mycobacterias atrasa el diagnóstico y se acelera el deterioro clínico del paciente.

Abstract The nontuberculous mycobacteria are rarely recognized today in the world, being increased their prevalence about to departure of their suspicion in chronic illnesses such as inmunocompromised patients and cystic fibrosis. We present a case with diagnosis of syndrome of Lady Windermere about to departure of a square of chronic cough. Computed tomography was performed where bilateral bronchiectasis is observed in the left lingual segment and right upper lobe. In the Bronchoscopy was isolated complex Mycobacterium avium-intracellulare. The lack of suspicion of nontuberculous mycobacteria in patient without risk factors, with a square of chronic cough leads to the delay in the diagnosis and the patient's clinical deterioration.

Cough suppression disorders spectrum.

Volitional cough suppression, identified exclusively in females, is an unusual causal mechanism for instances of lobar atalectasis and bronchiectasis. It is a postulated mechanism for the genesis of Lady Windermere Syndrome.