Dr. Stephen Ruoss specializes in both critical care medicine and pulmonary medicine. His pulmonary medicine clinical practice includes a focus the treatment of chronic bronchiectasis and mycobacterial lung infections, and also on rare lung diseases, including lymphangioleiomyomatosis (LAM). He has practiced in academic pulmonary and critical care medicine for over 20 years.

Clinical Focus

  • Critical Care Medicine
  • Pulmonology (Lung) and Critical Care

Academic Appointments

Administrative Appointments

  • Medical Director, Stanford Medical Center Respiratory Care Services, Stanford Medical Center (2004 - Present)
  • Medical Director, Stanford Medical Center Transfer Center, Stanford Medical Center (2003 - Present)
  • Clinical Chief, Pulmonary and Critical Care Medicine Division, Department of Medicine (2010 - Present)

Professional Education

  • Board Certification: American Board of Internal Medicine, Critical Care Medicine
  • Residency: Boston University Medical Center Internal Medicine Residency (1984) MA
  • Internship: University of Connecticut Internal Medicine Residency (1982) CT
  • Board Certification: American Board of Internal Medicine, Pulmonary Disease (1990)
  • Residency: VA Medical Center Boston (1985) MA
  • Fellowship: UCSF Medical Center (1991) CA
  • Board Certification: American Board of Internal Medicine, Internal Medicine (1984)
  • Medical Education: University of Washington School of Medicine (1981) WA
  • MD, University of Washington, Medicine (1981)

Current Research and Scholarly Interests

We have an active collaborative project examining basic and clinical aspects of non-tuberculous mycobacterial (NTM) lung infection in non-immune compromised adults. Studies have examined possible cellular immune mechanisms for increased susceptibility to these infections, and are also investigating aspects of optimal diagnosis and treatment. In addition, a clinical and translational research program is investigating the causes and genetic factors underlying the evolution of bronchiectasis. Projects include genetic susceptibility in bronchiectasis, as well as therapy projects for adults with pulmonary NTM infections.

Clinical Trials

  • Safety and Efficacy of Saracatinib In Subjects With Lymphangioleiomyomatosis Recruiting

    This study is being done to determine if there is a potential benefit of saracatinib in LAM subjects. Based on the information of this trial, additional clinical development trials will be needed. The study will also test the tolerability of 125 mg of saracatinib given once daily over a 9 month period.

    View full details

  • Comparison of Two- Versus Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease Not Recruiting

    NTM therapy consists of a multi-drug macrolide based regimen for 18-24 months. Treated patients frequently experience debilitating side effects, and many patients delay the start of antibiotic treatment due to these risks. Common side effects include nausea, diarrhea, and fatigue, and rare but serious toxicities include ocular toxicity, hearing loss, and hematologic toxicity. To date, most of the evidence underlying the current treatment recommendations has come from observational studies in which either a macrolide has been combined with rifampin and ethambutol, or in some cases combined with ethambutol alone. The proposed study will answer whether a third drug is necessary or whether taking two drugs can increase tolerability without a substantial loss of efficacy.

    Stanford is currently not accepting patients for this trial.

    View full details

2023-24 Courses

All Publications

  • Management of nontuberculous mycobacteria in lung transplant cases: an international Delphi study. ERJ open research Asif, H., Rahaghi, F. F., Ohsumi, A., Philley, J., Emtiazjoo, A., Hirama, T., Baker, A. W., Shu, C., Silveira, F., Poulin, V., Rizzuto, P., Nagao, M., Burgel, P., Hays, S., Aksamit, T., Kawasaki, T., Dela Cruz, C., Aliberti, S., Nakajima, T., Ruoss, S., Marras, T. K., Snell, G. I., Winthrop, K., Mirsaeidi, M. 2023; 9 (2)


    Rationale: Nontuberculous mycobacterial (NTM) diseases are difficult-to-treat infections, especially in lung transplant (LTx) candidates. Currently, there is a paucity of recommendations on the management of NTM infections in LTx, focusing on Mycobacterium avium complex (MAC), M. abscessus and M. kansasii.Methods: Pulmonologists, infectious disease specialists, LTx surgeons and Delphi experts with expertise in NTM were recruited. A patient representative was also invited. Three questionnaires comprising questions with multiple response statements were distributed to panellists. Delphi methodology with a Likert scale of 11 points (5 to -5) was applied to define the agreement between experts. Responses from the first two questionnaires were collated to develop a final questionnaire. The consensus was described as a median rating >4 or <-4 indicating for or against the given statement. After the last round of questionnaires, a cumulative report was generated.Results: Panellists recommend performing sputum cultures and a chest computed tomography scan for NTM screening in LTx candidates. Panellists recommend against absolute contraindication to LTx even with multiple positive sputum cultures for MAC, M. abscessus or M. kansasii. Panellists recommend MAC patients on antimicrobial treatment and culture negative can be listed for LTx without further delay. Panellists recommend 6 months of culture-negative for M. kansasii, but 12 months of further treatment from the time of culture-negative for M. abscessus before listing for LTx.Conclusion: This NTM LTx study consensus statement provides essential recommendations for NTM management in LTx and can be utilised as an expert opinion while awaiting evidence-based contributions.

    View details for DOI 10.1183/23120541.00377-2022

    View details for PubMedID 37009016

  • IMPACT OF C-REACTIVE PROTEIN ON ANTICOAGULATION MONITORING IN EXTRACORPOREAL MEMBRANE OXYGENATION Madhok, J., ODonnell, C., Jin, J., Owyang, C., Weimer, J., Pashun, R., Shudo, Y., McNulty, J., Chadwick, B., Ruoss, S., Rao, V., Zehnder, J., Hsu, J. LIPPINCOTT WILLIAMS & WILKINS. 2023: 54
  • Severe COVID-19 disease in a 2nd trimester pregnancy: Successful ECMO and mechanical ventilation management. Respiratory medicine case reports Hansra, B. S., Rao, V. K., Vogelsong, M. A., Ruoss, S. J. 2022; 39: 101721


    Extracorporeal membrane oxygenation (ECMO) is an invasive support strategy for cardiac, respiratory, or combined cardiorespiratory failure. ECMO has become increasing utilized in patients with severe respiratory failure due to COVID-19 infection. To our knowledge there is no report of successful ECMO utilization in second trimester of pregnancy leading to a successful outcome. We present a case of severe COVID-19 infection in a patient causing respiratory failure in the second trimester pregnancy. With diligent utilization of ECMO and mechanical ventilation we were able to support the patient's respiratory needs to allow her pregnancy to continue. Ultimately, the patient underwent successful caesarean section in the third trimester. This case highlights excellent lung injury protection and lung recovery can be achieved through optimal utilization of ECMO support together with a careful and closely monitored lung protective ventilation strategy, even while also supporting the patient through the increasing metabolic circumstances of a progressing pregnancy.

    View details for DOI 10.1016/j.rmcr.2022.101721

    View details for PubMedID 35965487

  • Unexpected Interruptions in the Inhaled Epoprostenol Delivery System: Incidence of Adverse Sequelae and Therapeutic Consequences in Critically Ill Patients. Critical care explorations Block, J. M., Madhok, J., Owyang, C. G., Merriman, K. R., Ruoss, S. J., Rao, V. K. 2021; 3 (10): e0548


    OBJECTIVES: Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients.DESIGN: Retrospective review and analysis.SETTING: Stanford University Hospital, a 605-bed tertiary care center.PATIENTS: Patients receiving inhaled epoprostenol in 2019.INTERVENTIONS: No interventions.MEASUREMENTS AND MAIN RESULTS: Clinical indication, duration of inhaled epoprostenol delivery, mode of respiratory support, and documented unexpected interruption. In 2019, there were 493 administrations of inhaled epoprostenol in 433 unique patients. Primary indications for inhaled epoprostenol were right heart dysfunction (n = 394; 79.9%) and hypoxemia (n = 92; 18.7%). Unexpected delivery interruptions occurred in 31 administrations (6.3%). Median duration of therapy prior to unexpected interruption was 2 days (interquartile range, 2-5 d). Respiratory support at the time of unexpected interruption was mechanical ventilation (61.3%), high-flow nasal cannula (35.5%), and noninvasive positive pressure ventilation (3.2%). Adverse sequelae of unexpected interruption included elevated pulmonary artery pressures (n = 12), systemic hypotension (n = 8), hypoxemia (n = 8), elevated central venous pressure (n = 4), and cardiac arrest (n = 1). Therapeutic interventions following unexpected interruption included initiation of inhaled nitric oxide (n = 21), increase in vasoactive medication (n = 2), and increase in respiratory support (n = 2). Most of the adverse events were Common Terminology Criteria for Adverse Events grade 3 and 4 (93.5%).CONCLUSIONS: A retrospective review of patients receiving inhaled epoprostenol via vibrating mesh nebulizer in 2019 revealed interruptions in 6.3% of administrations with most of these interruptions requiring therapeutic intervention. The true incidence of unexpected interruption and subsequent rate of unexpected interruption's requiring intervention is unknown due to the reliance on unexpected interruption identification and subsequent documentation in the electronic medical record. Sudden interruption in inhaled epoprostenol delivery can result in severe cardiopulmonary compromise, and on rare occasion, death.

    View details for DOI 10.1097/CCE.0000000000000548

    View details for PubMedID 34671745

  • Utility Of Cardiopulmonary Exercise Testing In Chronic Unexplained Dyspnea In A 77 Year Old Female Christle, J. W., Andruska, A. M., Moneghetti, K. J., Wheeler, M. T., Ashley, E. A., Myers, J., Ruoss, S. LIPPINCOTT WILLIAMS & WILKINS. 2021: 395
  • Antithrombin in Extracorporeal Membrane Oxygenation: To Replenish or Not to Replenish? Critical care medicine Madhok, J., Ruoss, S. J. 2021; 49 (4): e480–e481

    View details for DOI 10.1097/CCM.0000000000004812

    View details for PubMedID 33731637

  • The Pathophysiology and Dangers of Silent Hypoxemia in COVID-19 Lung Injury. Annals of the American Thoracic Society Swenson, K. E., Ruoss, S. J., Swenson, E. R. 2021


    The ongoing COVID-19 pandemic has been unprecedented on many levels, not least of which are the challenges in understanding the pathophysiology of these new critically ill patients. One widely-reported phenomenon is that of a profoundly hypoxemic patient with minimal to no dyspnea out of proportion to the extent of radiographic abnormalities and changes in lung compliance. This apparently unique presentation, sometimes called "happy hypoxemia or hypoxia" but better described as "silent hypoxemia", has led to the speculation of underlying pathophysiologic differences between COVID-19 lung injury and ARDS from other causes. We explore three proposed distinctive features of COVID-19 that likely bear on the genesis of silent hypoxemia, including differences in lung compliance, pulmonary vascular responses to hypoxia, and nervous system sensing and response to hypoxemia. In the context of known principles of respiratory physiology and neurobiology, we discuss whether these particular findings are due to direct viral effects or, equally plausible, are within the spectrum of typical ARDS pathophysiology and the wide range of hypoxic ventilatory and pulmonary vascular responses, and dyspnea perception in healthy people. Comparisons between lung injury patterns in COVID-19 and other causes of ARDS are clouded by the extent and severity of this pandemic, which may underlie the description of "new" phenotypes while limiting our ability to confirm these phenotypes by more invasive and longitudinal studies. However, given the uncertainty about anything unique in the pathophysiology of COVID-19 lung injury, there are no compelling pathophysiologic reasons at present to support a different therapeutic approach for these patients to the proven standards of care in ARDS.

    View details for DOI 10.1513/AnnalsATS.202011-1376CME

    View details for PubMedID 33621159

  • Active surveillance of serious adverse events following transfusion of COVID-19 convalescent plasma. Transfusion Swenson, E., Wong, L. K., Jhaveri, P., Weng, Y., Kappagoda, S., Pandey, S., Pritchard, A., Rogers, A., Ruoss, S., Subramanian, A., Shan, H., Hollenhorst, M. 2021


    The reported incidence of adverse reactions following Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) transfusion has generally been lower than expected based on the incidence of transfusion reactions that have been observed in studies of conventional plasma transfusion. This raises the concern for under-reporting of adverse events in studies of CCP that rely on passive surveillance strategies.Our institution implemented a protocol to actively identify possible adverse reactions to CCP transfusion. In addition, we retrospectively reviewed the charts of inpatients who received CCP at Stanford Hospital between May 13, 2020 and January 31, 2021. We determined the incidence of adverse events following CCP transfusion.A total of 49 patients received CCP. Seven patients (14%) had an increased supplemental oxygen requirement within 4 h of transfusion completion, including one patient who was intubated during the transfusion. An additional 11 patients (total of 18, 37%) had increased oxygen requirements within 24 h of transfusion, including 3 patients who were intubated. Six patients (12%) fulfilled criteria for transfusion-associated circulatory overload (TACO).Using an active surveillance strategy, we commonly observed adverse events following the transfusion of CCP to hospitalized patients. It was not possible to definitively determine whether or not these adverse events are related to CCP transfusion. TACO was likely over-diagnosed given overlap with the manifestations of COVID-19. Nevertheless, these results suggest that the potential adverse effects of CCP transfusion may be underestimated by reports from passive surveillance studies.

    View details for DOI 10.1111/trf.16711

    View details for PubMedID 34677830

  • Correction: Low-level mosaicism in tuberous sclerosis complex: prevalence, clinical features, and risk of disease transmission. Genetics in medicine : official journal of the American College of Medical Genetics Giannikou, K., Lasseter, K. D., Grevelink, J. M., Tyburczy, M. E., Dies, K. A., Zhu, Z., Hamieh, L., Wollison, B. M., Thorner, A. R., Ruoss, S. J., Thiele, E. A., Sahin, M., Kwiatkowski, D. J. 2020

    View details for DOI 10.1038/s41436-020-01066-w

    View details for PubMedID 33353975

  • Reamed Intramedullary Nailing of a Femur Fracture in a Polytraumatized Patient on Extracorporeal Membrane Oxygenation: A Case Report. JBJS case connector Bosch, L., Ruoss, S., Bishop, J. 2020; 10 (1): e0349


    CASE: We present the case of a young adult with blunt lung trauma and acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO) after a motor vehicle crash with a concomitant diaphyseal femur fracture who underwent reamed intramedullary nailing (IMN) while on ECMO support.CONCLUSION: This case is important because it demonstrates that reamed IMN of the femur has been performed safely in a critically ill patient on ECMO.

    View details for DOI 10.2106/JBJS.CC.19.00349

    View details for PubMedID 32044786

  • Amikacin Liposome Inhalation Suspension for MAC Lung Disease: A 12-Month Open-Label Extension Study. Annals of the American Thoracic Society Winthrop, K. L., Flume, P. A., Thomson, R. n., Mange, K. C., Yuen, D. W., Ciesielska, M. n., Morimoto, K. n., Ruoss, S. J., Codecasa, L. R., Yim, J. J., Marras, T. K., van Ingen, J. n., Wallace, R. J., Brown-Elliott, B. A., Coulter, C. n., Griffith, D. E. 2020


    Patients with refractory Mycobacterium avium complex (MAC) lung disease have limited treatment options. In the CONVERT study, amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) increased culture conversion rates vs GBT alone by Month 6. Limited data are available regarding >6-month treatment in a refractory population.Evaluate 12-month safety, tolerability, and efficacy of ALIS+GBT.Adults with refractory MAC lung disease not achieving culture conversion by CONVERT Month 6 could enroll in this open-label extension (INS-312) to receive 590 mg once-daily ALIS+GBT for 12 months. Two cohorts enrolled: the "ALIS-naive" cohort included patients randomized to GBT alone in CONVERT, and the "prior-ALIS" cohort included those randomized to ALIS+GBT in CONVERT. Safety and tolerability of ALIS over 12 months (primary endpoint) and culture conversion by Months 6 and 12 were assessed.In the ALIS-naive cohort, 83.3% of patients (n=75/90) experienced respiratory treatment-emergent adverse events (TEAEs), and 35.6% (n=32) had serious TEAEs; 26.7% (n=24) achieved culture conversion by Month 6 and 33.3% (n=30) by Month 12. In the prior-ALIS cohort, 46.6% of patients (n=34/73) experienced respiratory TEAEs, and 27.4% (n=20) had serious TEAEs; 9.6% (n=7) achieved culture conversion by Month 6 (≤14 months ALIS exposure) and 13.7% (n=10) by Month 12 (≤20 months ALIS exposure). Nephrotoxicity-related TEAEs and measured hearing decline were infrequent in both cohorts.In up to 20 months of ALIS use, respiratory TEAEs were common, nephrotoxicity and hearing decline were infrequent, and culture conversion continued beyond 6 months of therapy. Clinical trial registered with (NCT02628600).

    View details for DOI 10.1513/AnnalsATS.202008-925OC

    View details for PubMedID 33326356

  • Clevidipine-Induced Extreme Hypoxemia in a Neurosurgical Patient: A Case Report. A&A practice Short, J. H., Fatemi, P., Ruoss, S., Angelotti, T. 2019


    Clevidipine-induced pulmonary shunting is a little-reported adverse effect, manifesting as refractory hypoxemia, which may cause significant patient harm. We present the case of a mechanically ventilated patient admitted to the intensive care unit following a neurosurgical procedure. He was treated postoperatively with clevidipine for blood pressure management, and within 16 hours, he developed profound refractory hypoxemia, requiring increased ventilatory support. A workup for other causes was negative. The hypoxemia recovered within 1 hour of clevidipine discontinuation. Though other calcium channel blockers have been reported to cause pulmonary shunting from vasodilation, this is a novel case report for clevidipine-induced hypoxemia.

    View details for DOI 10.1213/XAA.0000000000001146

    View details for PubMedID 31770132

  • The NHLBI LAM Registry Prognostic Physiologic and Radiologic Biomarkers Emerge From a 15-Year Prospective Longitudinal Analysis CHEST Gupta, N., Lee, H., Ryu, J. H., Taveira-DaSilva, A. M., Beck, G. J., Lee, J., McCarthy, K., Finlay, G. A., Brown, K. K., Ruoss, S. J., Avila, N. A., Moss, J., McCormack, F. X., NHLBI LAM Registry Grp 2019; 155 (2): 288–96
  • The NHLBI LAM Registry: Prognostic Physiologic and Radiologic Biomarkers Emerge From a 15-Year Prospective Longitudinal Analysis. Chest Gupta, N., Lee, H., Ryu, J. H., Taveira-DaSilva, A. M., Beck, G. J., Lee, J., McCarthy, K., Finlay, G. A., Brown, K. K., Ruoss, S. J., Avila, N. A., Moss, J., McCormack, F. X., NHLBI LAM Registry Group 2019; 155 (2): 288–96


    BACKGROUND: The natural history of lymphangioleiomyomatosis (LAM) is mainly derived from retrospective cohort analyses, and it remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM.METHODS: A linear mixed effects model was used to compute the rate of decline of FEV1 and to identify variables affecting FEV1 decline among 217 registry patients who enrolled from 1998 to 2001. Prognostic variables associated with progression to death/lung transplantation were identified by using a Cox proportional hazards model.RESULTS: Mean annual decline of FEV1 was 89 ± 53mL/year and remained remarkably constant regardless of baseline lung function. FEV1 decline was more rapid in those with greater cyst profusion on CT scanning (P= .02) and in premenopausal subjects (118mL/year) compared with postmenopausal subjects (74mL/year) (P= .003). There were 26 deaths and 43 lung transplantations during the evaluation period. The estimated 5-, 10-, 15-, and 20-year transplant-free survival rates were 94%, 85%, 75%, and 64%, respectively. Postmenopausal status (hazard ratio, 0.30; P= .0002) and higher baseline FEV1 (hazard ratio, 0.97; P= .008) or diffusion capacity of lung for carbon monoxide (hazard ratio, 0.97; P= .001) were independently associated with a lower risk of progression to death or lung transplantation.CONCLUSIONS: The median transplant-free survival in patients with LAM is > 20 years. Menopausal status, as well as structural and physiologic markers of disease severity, significantly affect the rate of decline of FEV1 and progression to death or lung transplantation in LAM.

    View details for PubMedID 29940164

  • Low-level mosaicism in tuberous sclerosis complex: prevalence, clinical features, and risk of disease transmission. Genetics in medicine : official journal of the American College of Medical Genetics Giannikou, K. n., Lasseter, K. D., Grevelink, J. M., Tyburczy, M. E., Dies, K. A., Zhu, Z. n., Hamieh, L. n., Wollison, B. M., Thorner, A. R., Ruoss, S. J., Thiele, E. A., Sahin, M. n., Kwiatkowski, D. J. 2019


    To examine the prevalence and spectrum of mosaic variant allele frequency (MVAF) in tuberous sclerosis complex (TSC) patients with low-level mosaicism and correlate genetic findings with clinical features and transmission risk.Massively parallel sequencing was performed on 39 mosaic TSC patients with 170 different tissue samples.TSC mosaic patients (MVAF: 0-10%, median 1.7% in blood DNA) had a milder and distinct clinical phenotype in comparison with other TSC series, with similar facial angiofibromas (92%) and kidney angiomyolipomas (83%), and fewer seizures, cortical tubers, and multiple other manifestations (p < 0.0001 for six features). MVAF of TSC1/TSC2 pathogenic variants was highly variable in different tissue samples. Remarkably, skin lesions were the most reliable tissue for variant identification, and 6 of 39 (15%) patients showed no evidence of the variant in blood. Semen analysis showed absence of the variant in 3 of 5 mosaic men. The expected distribution of MVAF in comparison with that observed here suggests that there is a considerable number of individuals with low-level mosaicism for a TSC2 pathogenic variant who are not recognized clinically.Our findings provide information on variability in MVAF and risk of transmission that has broad implications for other mosaic genetic disorders.

    View details for DOI 10.1038/s41436-019-0562-6

    View details for PubMedID 31160751

  • Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT) AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Griffith, D. E., Eagle, G., Thomson, R., Aksamit, T. R., Hasegawa, N., Morimoto, K., Addrizzo-Harris, D. J., O'Donnell, A. E., Marras, T. K., Flume, P. A., Loebinger, M. R., Morgan, L., Codecasa, L. R., Hill, A. T., Ruoss, S. J., Yim, J., Ringshausen, F. C., Field, S. K., Philley, J. V., Wallace, R. J., van Ingen, J., Coulter, C., Nezamis, J., Winthrop, K. L., CONVERT Study Grp 2018; 198 (12): 1559–69
  • Association between Inhaled Corticosteroid Use and Pulmonary Nontuberculous Mycobacterial Infection ANNALS OF THE AMERICAN THORACIC SOCIETY Liu, V. X., Winthrop, K. L., Lu, Y., Sharifi, H., Nasiri, H. U., Ruoss, S. J. 2018; 15 (10): 1169–76


    Nontuberculous mycobacterial (NTM) pulmonary disease prevalence is increasing.To determine the association between the use of inhaled corticosteroids and the likelihood of NTM pulmonary infection among individuals with treated airway disease.We conducted a case-control study of subjects with airway disease with and without NTM pulmonary infection (based on mycobacterial respiratory cultures) between 2000 and 2010 in northern California. We quantified the use of inhaled corticosteroids, other airway disease medications, and healthcare use within 6 months of NTM pulmonary infection identification. We used 1:10 case-control matching and conditional logistic regression to evaluate the association between the duration and cumulative dosage of inhaled corticosteroid use and NTM pulmonary infection.We identified 248 cases with NTM pulmonary infection with an estimated rate of 16.4 cases per 10,000 subjects treated for airway disease. The median interval between treated airway disease cohort entry (defined as date of patient filling the third airway disease treatment prescription) and NTM case identification was 1,217 days. Compared with control subjects, subjects with NTM pulmonary infection were more likely to use airway disease medications including systemic steroids; they were also more likely to use health care. Any inhaled corticosteroids use between 120 days and 2 years before cohort entry was associated with substantially increased odds of NTM infection. For example, the adjusted odds ratio for NTM infection among inhaled corticosteroid users in a 2-year interval was 2.51 (95% confidence interval, 1.40-4.49; P < 0.01). Increasing cumulative inhaled corticosteroid dose was also associated with greater odds of NTM infection.Inhaled corticosteroid use, and particularly high-dose inhaled corticosteroid use, was associated with an increased risk of NTM pulmonary infection.

    View details for PubMedID 30213194

  • Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT): A Prospective, Open-Label, Randomized Study. American journal of respiratory and critical care medicine Griffith, D. E., Eagle, G., Thomson, R., Aksamit, T. R., Hasegawa, N., Morimoto, K., Addrizzo-Harris, D. J., O'Donnell, A. E., Marras, T. K., Flume, P. A., Loebinger, M. R., Morgan, L., Codecasa, L. R., Hill, A. T., Ruoss, S. J., Yim, J., Ringshausen, F. C., Field, S. K., Philley, J. V., Wallace, R. J., van Ingen, J., Coulter, C., Nezamis, J., Winthrop, K. L., CONVERT Study Group 2018


    Rationale Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite ≥6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS+GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as 3 consecutive monthly MAC-negative sputum cultures by month 6. Measurements and Main Results Enrolled patients (ALIS+GBT, n=224; GBT-alone, n=112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS+GBT and 10 of 112 (8.9%) with GBT alone (OR, 4.22; 95% CI [2.08, 8.57]; P<0.001). Patients in the ALIS+GBT arm vs GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% CI, [2.00, 7.60]). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS+GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registration available at, ID NCT02344004.

    View details for PubMedID 30216086

  • A Phase II Clinical Trial of an Aromatase Inhibitor for Postmenopausal Women with Lymphangioleiomyomatosis. Annals of the American Thoracic Society Lu, C., Lee, H., Pappas, G. P., Dilling, D. F., Burger, C. D., Shifren, A., Veeraraghavan, S., Chapman, J. T., Parambil, J., Ruoss, S. J., Young, L. R., Hammes, S. R., Kopras, E. J., Roads, T., Krischer, J. P., McCormack, F. X. 2017; 14 (6): 919-928


    Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease that predominantly affects women and can worsen with pregnancy, estrogen treatment, and the menstrual cycle, suggesting an important role for estrogen in disease pathogenesis.To assess the efficacy and safety of the aromatase inhibitor letrozole in the treatment of LAM.Seventeen postmenopausal women with LAM were enrolled in this phase II trial and randomized to receive letrozole 2.5 mg daily (n = 9) or placebo (n = 8) for a period of 12 months. Five patients in each group were also taking sirolimus at baseline and remained on the drug throughout the treatment period. Lung function, exercise capacity, quality of life, and serum vascular endothelial growth factor D (VEGF-D) were measured at baseline and at 3-month intervals.Fifteen patients completed the study. Two patients withdrew. There were no differences in adverse events in the letrozole and placebo groups. The target enrollment of 25 patients per arm was not met, so the efficacy of letrozole could not be assessed as planned. After adjusting for sirolimus use, we found that the rate of change in FEV1 for all subjects was -3 ± 3 ml/mo (P = 0.4), and for serum VEGF-D, the rate of change was -0.024 ± 0.009 pg/ml/mo (P = 0.015), showing a steeper decline in the letrozole group (-0.029 ± 0.013; P = 0.025). All patients who were taking sirolimus had a reduction in VEGF-D levels from baseline to the last visit, compared with only half of the patients who were not taking sirolimus. In a post hoc analysis, eight matched letrozole-treated-placebo-treated pairs were constructed, six of which demonstrated better FEV1 improvement for the letrozole-treated patients.Letrozole treatment appears to be safe and well tolerated in postmenopausal patients with LAM, including those taking sirolimus. Enrollment in this trial was compromised by the publication of an effective treatment (sirolimus) in the same month as the study opened, resulting in limited power to detect treatment effects. Post hoc matched pairs exploration studies provide tentative support for additional studies of letrozole in LAM. Considering the reduced rate of lung function decline in postmenopausal patients, future studies will likely require enhanced study designs, such as selective enrollment of those with prognostic biomarkers predictive of decline. Clinical trial registered with (NCT01353209).

    View details for DOI 10.1513/AnnalsATS.201610-824OC

    View details for PubMedID 28570161

  • Randomized Trial of Liposomal Amikacin for Inhlation in Nontuberculous Mycobacterial Lung Disease AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Olivier, K. N., Griffith, D. E., Eagle, G., McGinnis, J. P., Micioni, L., Liu, K., Daley, C. L., Winthrop, K. L., Ruoss, S., Addrizzo-Harris, D. J., Flume, P. A., Dorgan, D., Salathe, M., Brown-Elliott, B. A., Gupta, R., Wallace, R. J. 2017; 195 (6): 814-823


    Rationale Lengthy multi-drug, toxic, and low efficacy regimens limit management of pulmonary nontuberculous mycobacterial (PNTM) disease. Objective This phase 2 study investigated efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory PNTM (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. Methods During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multi-drug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. Primary endpoint was change from baseline to day 84 on a semi-quantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute walk distance, and adverse events. Measurements and Main Results Modified intent-to-treat population included 89 (LAI=44; placebo=45) patients. Average age was 59 years, 88% were female, 92% were Caucasian; 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. Primary endpoint was not achieved (P=0.072); however, a greater proportion of the LAI group demonstrated ≥1 negative sputum cultures (32% [14/44] vs. 9% [4/45]; P=0.006) and improvement in 6-minute walk test (+20.6 vs. -25.0 meters; P=0.017) at day 84. Treatment effect was predominantly in patients without cystic fibrosis with MAC and was sustained 1 year post-LAI. Most adverse events were respiratory and in some patients led to drug discontinuation. Conclusions Although the primary endpoint was not reached, LAI added to a multi-drug regimen produced improvements in sputum conversion and 6-minute walk distance vs. placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research is needed. Clinical trial registration available at, ID NCT01315236.

    View details for DOI 10.1164/rccm.201604-0700OC

    View details for Web of Science ID 000396640500016

  • Randomized Trial of Liposomal Amikacin for Inhalation in Nontuberculous Mycobacterial Lung Disease. American journal of respiratory and critical care medicine Olivier, K. N., Griffith, D. E., Eagle, G., McGinnis Ii, J. P., Micioni, L., Liu, K., Daley, C. L., Winthrop, K. L., Ruoss, S., Addrizzo-Harris, D. J., Flume, P. A., Dorgan, D., Salathe, M., Brown-Elliott, B. A., Gupta, R., Wallace, R. J. 2016: -?


    Rationale Lengthy multi-drug, toxic, and low efficacy regimens limit management of pulmonary nontuberculous mycobacterial (PNTM) disease. Objective This phase 2 study investigated efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory PNTM (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. Methods During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multi-drug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. Primary endpoint was change from baseline to day 84 on a semi-quantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute walk distance, and adverse events. Measurements and Main Results Modified intent-to-treat population included 89 (LAI=44; placebo=45) patients. Average age was 59 years, 88% were female, 92% were Caucasian; 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. Primary endpoint was not achieved (P=0.072); however, a greater proportion of the LAI group demonstrated ≥1 negative sputum cultures (32% [14/44] vs. 9% [4/45]; P=0.006) and improvement in 6-minute walk test (+20.6 vs. -25.0 meters; P=0.017) at day 84. Treatment effect was predominantly in patients without cystic fibrosis with MAC and was sustained 1 year post-LAI. Most adverse events were respiratory and in some patients led to drug discontinuation. Conclusions Although the primary endpoint was not reached, LAI added to a multi-drug regimen produced improvements in sputum conversion and 6-minute walk distance vs. placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research is needed. Clinical trial registration available at, ID NCT01315236.

    View details for PubMedID 27748623

  • Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases EUROPEAN RESPIRATORY JOURNAL Gupta, N., Meraj, R., Tanase, D., James, L. E., Seyama, K., Lynch, D. A., Akira, M., Meyer, C. A., Ruoss, S. J., Burgers, C. D., Young, L. R., Almoosa, K. F., Veeraraghavan, S., Barker, A. F., Lee, A. S., Dilling, D. F., Inoue, Y., Cudzilo, C. J., Zafar, M. A., McCormack, F. X. 2015; 46 (4): 1196–99

    View details for PubMedID 26160866

  • 3B. Personal History: Have You Ever Had Excessive Shortness of Breath or Fatigue with Exercise beyond What Is Expected for Your Level of Fitness? CURRENT SPORTS MEDICINE REPORTS Kenny, J. S., Ruoss, S. 2015; 14 (3): 259-260

    View details for Web of Science ID 000354551400029

    View details for PubMedID 25968868

  • Acute cellular insulin resistance and hyperglycemia associated with hypophosphatemia after cardiac surgery. A & A case reports Garazi, E., Bridge, S., Caffarelli, A., Ruoss, S., van der Starre, P. 2015; 4 (2): 22-25


    Successful glycemic control reduces morbidity and mortality in cardiac surgery patients. Protocols that include insulin infusions are commonly followed to achieve target blood glucose levels. Insulin resistance has been reported and linked to low serum phosphate levels in animal models and studies in diabetic outpatients, but not in postoperative patients. The following case series is a retrospective observational review of 8 cardiac surgery patients who developed insulin resistance early after surgery; this resistance was reversed by correcting serum hypophosphatemia. We discuss the multiple underlying mechanisms causing hypophosphatemia.

    View details for DOI 10.1213/XAA.0000000000000112

    View details for PubMedID 25611002

  • Consequences of Federal Patient Transfer Regulations: Effect of the 2003 EMTALA Revision on a Tertiary Referral Center and Evidence of Possible Misuse ARCHIVES OF INTERNAL MEDICINE Kao, D. P., Martin, M. H., Das, A. K., Ruoss, S. J. 2012; 172 (11): 891-892

    View details for Web of Science ID 000305087600015

    View details for PubMedID 22688995

    View details for PubMedCentralID PMC3507997

  • Diagnosing invasive fungal disease in critically ill patients CRITICAL REVIEWS IN MICROBIOLOGY Hsu, J. L., Ruoss, S. J., Bower, N. D., Lin, M., Holodniy, M., Stevens, D. A. 2011; 37 (4): 277-312


    Fungal infections are increasing, with a changing landscape of pathogens and emergence of new groups at risk for invasive disease. We review current diagnostic techniques, focusing on studies in critically ill patients. Microbiological cultures, the current "gold standard", demonstrate poor sensitivity, thus diagnosis of invasive disease in the critically ill is difficult. This diagnostic dilemma results in under- or over-treatment of patients, potentially contributing to poor outcomes and antifungal resistance. While other current diagnostic tests perform moderately well, many lack timeliness, efficacy, and are negatively affected by treatments common to critically ill patients. New nucleic acid-based research is promising.

    View details for DOI 10.3109/1040841X.2011.581223

    View details for Web of Science ID 000295616800001

    View details for PubMedID 21749278

  • A LOW COST ALTERNATIVE FOR MECHANICAL VENTILATION IN LARGE SCALE DISASTERS 40th Critical Care Congress Callaghan, M., Boddupalli, D., Yock, P., Krummel, T., Ruoss, S. LIPPINCOTT WILLIAMS & WILKINS. 2010: U252–U252
  • The International LAM Registry: A Component of an Innovative Web-Based Clinician, Researcher, and Patient-Driven Rare Disease Research Platform LYMPHATIC RESEARCH AND BIOLOGY Nurok, M., Eslick, I., Carvalho, C. R., Costabel, U., D'Armiento, J., Glanville, A. R., Harari, S., Henske, E. P., Inoue, Y., Johnson, S. R., Lacronique, J., Lazor, R., Moss, J., Ruoss, S. J., Ryu, J. H., Seyama, K., Watz, H., Xu, K., Hohmann, E. L., Moss, F. 2010; 8 (1): 81-87


    A relative inability to capture a sufficiently large patient population in any one geographic location has traditionally limited research into rare diseases.Clinicians interested in the rare disease lymphangioleiomyomatosis (LAM) have worked with the LAM Treatment Alliance, the MIT Media Lab, and Clozure Associates to cooperate in the design of a state-of-the-art data coordination platform that can be used for clinical trials and other research focused on the global LAM patient population. This platform is a component of a set of web-based resources, including a patient self-report data portal, aimed at accelerating research in rare diseases in a rigorous fashion.Collaboration between clinicians, researchers, advocacy groups, and patients can create essential community resource infrastructure to accelerate rare disease research. The International LAM Registry is an example of such an effort. 82.

    View details for DOI 10.1089/lrb.2009.0028

    View details for Web of Science ID 000277870500011

    View details for PubMedID 20235890

  • Tuberculosis in Liver Transplant Recipients: A Systematic Review and Meta-Analysis of Individual Patient Data LIVER TRANSPLANTATION Holty, J. C., Gould, M. K., Meinke, L., Keeffe, E. B., Ruoss, S. J. 2009; 15 (8): 894-906


    Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid-related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short-term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18-fold increase in the prevalence of active MTB infection and a 4-fold increase in the case-fatality rate. For high-risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894-906, 2009. (c) 2009 AASLD.

    View details for DOI 10.1002/lt.21709

    View details for Web of Science ID 000268739200010

    View details for PubMedID 19642133

  • Successful pregnancy and cesarean delivery via noninvasive ventilation in mitochondrial myopathy JOURNAL OF PERINATOLOGY Yuan, N., El-Sayed, Y. Y., Ruoss, S. J., Riley, E., Enns, G. M., Robinson, T. E. 2009; 29 (2): 166-167


    We report a case study of a 22-year-old woman with mitochondrial thymidine kinase 2 deficiency and chronic respiratory failure due to severe neuromuscular weakness requiring noninvasive positive pressure ventilation (NIPPV) since 12 years of age. During pregnancy and cesarean delivery, she was successfully supported with NIPPV. A multidisciplinary team approach should be used in pregnant patients with these disorders with specific attention to management of pulmonary complications, selection of route of delivery, anesthesia, and analgesia.

    View details for DOI 10.1038/jp.2008.178

    View details for Web of Science ID 000263492700016

    View details for PubMedID 19177045

  • Coexistence of primary adenocarcinoma of the lung and Tsukamurella infection: a case report and review of the literature. Journal of medical case reports Perez, V. A., Swigris, J., Ruoss, S. J. 2008; 2: 207-?


    A major diagnostic challenge in the evaluation of a cavitary lung lesion is to distinguish between infectious and malignant etiologies.We present the case of an elderly man presenting with fever, hemoptysis and a left upper lobe cavitary lesion. Serial sputum cultures grew Tsukamurella pulmonis, a rare pathogen associated with cavitary pneumonia in immunocompromised patients. However, despite clinical improvement with antibiotic therapy targeted to the organism, concomitant discovery of a papillary thyroid carcinoma led to a needle biopsy of the cavitary lesion, which showed evidence of primary lung adenocarcinoma.This is the first description of Tsukamurella infection in the setting of primary lung carcinoma. The report also illustrates the potential complex nature of cavitary lesions and emphasizes the need to consider the coexistence of malignant and infectious processes in all patients, especially those with risk factors for malignancy that fail to improve on antibiotic therapy.

    View details for DOI 10.1186/1752-1947-2-207

    View details for PubMedID 18554413

    View details for PubMedCentralID PMC2442117

  • The safety and effects of the beta-blocker, nadolol, in mild asthma: An open-label pilot study PULMONARY PHARMACOLOGY & THERAPEUTICS Hanania, N. A., Singh, S., El-Wali, R., Flashner, M., Franklin, A. E., Garner, W. J., Dickey, B. F., Parra, S., Ruoss, S., Shardonofsky, F., O'Connor, B. J., Page, C., Bond, R. A. 2008; 21 (1): 134-141


    Beta-blockers are currently contraindicated in asthma because their acute administration may be associated with worsening bronchospasm. However, their effects and safety with their chronic administration are not well evaluated. The rationale for this pilot study was based on the paradigm shift that was observed with the use of beta-blockers in congestive heart failure, which once contraindicated because of their acute detrimental effects, have now been shown to reduce mortality with their chronic use. We hypothesized that certain beta-blockers may also be safe and useful in chronic asthma therapy. In this prospective, open-label, pilot study, we evaluated the safety and effects of escalating doses of the beta-blocker, nadolol, administered over 9 weeks to 10 subjects with mild asthma. Dose escalation was performed on a weekly basis based on pre-determined safety, lung function, asthma control and hemodynamic parameters. The primary objective was to evaluate safety and secondary objectives were to evaluate effects on airway hyperresponsiveness, and indices of respiratory function. The escalating administration of nadolol was well tolerated. In 8 out of the 10 subjects, 9 weeks of nadolol treatment produced a significant, dose-dependent increase in PC20 that reached 2.1 doubling doses at 40 mg (P<0.0042). However, there was also a dose-independent 5% reduction in mean FEV1 over the study period (P<0.01). We conclude that in most patients with mild asthma, the dose-escalating administration of the beta-blocker, nadolol, is well tolerated and may have beneficial effects on airway hyperresponsiveness. Our findings warrant further testing in future larger trials.

    View details for DOI 10.1016/j.pupt.2007.07.002

    View details for Web of Science ID 000262943300020

    View details for PubMedID 17703976

    View details for PubMedCentralID PMC2254137

  • Lung transplantation in the management of patients with lymphangioleiomyomatosis: Baseline data from the NHLBI LAM registry JOURNAL OF HEART AND LUNG TRANSPLANTATION Maurer, J. R., Ryu, J., Beck, G., Moss, J., Lee, J., Finlay, G., Brown, K., Chapman, J., McMahan, J., Olson, E., Ruoss, S., Sherer, S. 2007; 26 (12): 1293-1299


    In 1997, the National Heart, Lung, and Blood Institute of the National Institutes of Health established a Registry to better characterize the demographic, clinical, physiologic and radiographic features of patients with lymphangioleiomyomatosis (LAM). Herein we report data collected at enrollment from patients who had either undergone transplant prior to enrollment, underwent transplant during the 5-year study, or were evaluated/wait-listed for lung transplant during the 5-year study.The LAM Registry enrolled patients from six clinical centers between August 1998 and October 2001. On entry, patients filled-out questionnaires covering their medical history, symptoms, treatment and quality of life (SF-36 and St. George's Respiratory Questionnaire). Enrollees underwent blood laboratory work and testing for arterial blood gases and pulmonary function. Follow-up was done at 6-month and/or yearly intervals. Diagnoses were confirmed by biopsy or typical clinical presentation plus computerized tomography (CT) findings confirmed by independent expert radiologists. A total of 243 women were enrolled. Of these, 13 (5.3%) had been transplanted at time of entry (Group A), 21 (8.6%) were transplanted during the study (Group B), and 48 (19.8%) were either wait-listed for transplant or underwent evaluation after enrollment during the study period (Group C). The remaining 161 (66.3%) registrants were neither considered for nor listed for transplant during the Registry period (Group D).One-third of patients in a large sample of LAM patients had either been transplanted or were being considered for transplant. At enrollment, patients who had already been transplanted and those not in need of transplant (Groups A and D) had better pulmonary function and quality-of-life scores compared with patients who subsequently underwent lung transplant during the Registry period (Group B).In this large Registry of LAM patients, lung transplantation appears to be associated both with significantly improved lung function and quality of life compared with patients with advanced disease.

    View details for DOI 10.1016/j.healun.2007.09.013

    View details for Web of Science ID 000251993500010

    View details for PubMedID 18096481

    View details for PubMedCentralID PMC2276877

  • Aerosolized amikacin for treatment of pulmonary Mycobacterium avium infections: an observational case series. BMC pulmonary medicine Davis, K. K., Kao, P. N., Jacobs, S. S., Ruoss, S. J. 2007; 7: 2-?


    Current systemic therapy for nontuberculous mycobacterial pulmonary infection is limited by poor clinical response rates, drug toxicities and side effects. The addition of aerosolized amikacin to standard oral therapy for nontuberculous mycobacterial pulmonary infection may improve treatment efficacy without producing systemic toxicity. This study was undertaken to assess the safety, tolerability and preliminary clinical benefits of the addition of aerosolized amikacin to a standard macrolide-based oral treatment regimen.Six HIV-negative patients with Mycobacterium avium intracellulare pulmonary infections who had failed standard therapy were administered aerosolized amikacin at 15 mg/kg daily in addition to standard multi-drug macrolide-based oral therapy. Patients were monitored clinically and serial sputum cultures were obtained to assess response to therapy. Symptomatic improvement with radiographic stabilization and eradication of mycobacterium from sputum were considered markers of success. Of the six patients treated with daily aerosolized amikacin, five responded to therapy. All of the responders achieved symptomatic improvement and four were sputum culture negative after 6 months of therapy. Two patients became re-infected with Mycobacterium avium intracellulare after 7 and 21 months of treatment. One of the responders who was initially diagnosed with Mycobacterium avium intracellulare became sputum culture positive for Mycobacterium chelonae resistant to amikacin after being on intermittent therapy for 4 years. One patient had progressive respiratory failure and died despite additional therapy. There was no evidence of nephrotoxicity or ototoxicity associated with therapy.Aerosolized delivery of amikacin is a promising adjunct to standard therapy for pulmonary nontuberculous mycobacterial infections. Larger prospective trials are needed to define its optimal role in therapy of this disease.

    View details for PubMedID 17319962

  • Prospective analysis of cystic fibrosis transmembrane regulator mutations in adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection CHEST Ziedalski, T. M., Kao, P. N., Henig, N. R., Jacobs, S. S., Ruoss, S. J. 2006; 130 (4): 995-1002


    Bronchiectasis and pulmonary infection with nontuberculous mycobacteria (NTM) may be associated with disease-causing mutations in the cystic fibrosis transmembrane regulator (CFTR).Fifty adult patients at Stanford University Medical Center with a diagnosis of bronchiectasis and/or pulmonary NTM infection were prospectively characterized by sweat chloride measurement, comprehensive mutational analysis of CFTR, and sputum culture results.A de novo diagnosis of cystic fibrosis (CF) was established in 10 patients (20%). Patients with CF were more likely than those without CF to have mucus plugging seen on chest high-resolution CT, and women with a CF diagnosis were thinner, with a significantly lower mean body mass index than the non-CF subjects. Thirty CFTR mutations were identified in 24 patients (50% prevalence). Sweat chloride concentration was elevated > 60 mEq/dL (diagnostic of CF) in seven patients (14%), and from 40 to 60 mEq/dL in eight patients (16%). The frequency of CFTR mutations was elevated above that expected in the general population: heterozygous DeltaF508 (12% vs 3%), R75Q (14% vs 1%), and intron 8 5T (17% vs 5 to 10%). Other known CFTR mutations identified were V456A, G542X, R668C, I1027T, D1152, R1162L, W1282X, and L183I. Three novel CFTR mutations were identified: A394V, F650L, and C1344S.Mutations in CFTR that alter RNA splicing and/or functional chloride conductance are common in this population, and are likely to contribute to the susceptibility and pathogenesis of adult bronchiectasis and pulmonary NTM infection. Careful clinical evaluation for disease cause should be undertaken in this clinical context.

    View details for DOI 10.1378/chest.130.4.995

    View details for PubMedID 17035430

  • Factors related to response to intermittent treatment of Mycobacterium avium complex lung disease AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Lam, P. K., Griffith, D. E., Alksamit, T. R., Ruoss, S. J., Garay, S. M., Daley, C. L., Catanzaro, A. 2006; 173 (11): 1283-1289


    Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate. Objectives: To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin.A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000-2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-gamma treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed.Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5-11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7-9.2) and HRCT response by 4.9 times (95% CI, 1.9-13.0). Culture response was 1.5 times (95% CI, 1.1-2.2) higher for older subjects and 2.2 times (95% CI, 1.0-4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1-5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7-11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0-2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times.TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.

    View details for DOI 10.1164/rccm.200509-1531OC

    View details for Web of Science ID 000237990100018

    View details for PubMedID 16514112

  • Recurrence of pulmonary intravascular bronchoalveolar tumor with mediastinal metastasis 20 years later RESPIRATORY MEDICINE Chen, T. M., Donington, J., Mak, G., Berry, G. J., Ruoss, S. J., Rosen, G. D., Upadhyay, D. 2006; 100 (2): 367-370


    Pulmonary intravascular bronchoalveolar tumor (IVBAT) also recognized as pulmonary epithelioid hemangioendothelioma, is a rare malignant vascular tumor of unknown etiology. IVBAT is a tumor of multicentric origin and the lungs are rarely involved, with only about 60 cases of pulmonary IVBAT described in the literature. The prognosis is unpredictable, with life expectancy ranging from 1 to 15 years. We report an unusual case of pulmonary IVBAT that recurred in the lung with metastasis to the mediastinum.

    View details for DOI 10.1016/j.rmed.2005.05.010

    View details for Web of Science ID 000235243000024

    View details for PubMedID 15990286

  • The NHLBI lymphangioleiomyomatosis registry - Characteristics of 230 patients at enrollment AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Ryu, J. H., Moss, J., Beck, G. J., Lee, J. C., Brown, K. K., Chapman, J. T., Finlay, G. A., Olson, E. J., Ruoss, S. J., Maurer, J. R., Raffin, T. A., Peavy, H. H., McCarthy, K., Taveira-Da Silva, A., McCormack, F. X., Avila, N. A., DeCastro, R. M., Jacobs, S. S., Stylianou, M., Fanburg, B. L. 2006; 173 (1): 105-111


    Pulmonary lymphangioleiomyomatosis is a progressive cystic lung disease that is associated with infiltration of atypical smooth muscle-like cells. Previous descriptions of clinical characteristics of subjects with lymphangioleiomyomatosis have been based on a limited number of patients.To describe the clinical characteristics of subjects with pulmonary lymphangioleiomyomatosis, both sporadic and tuberous sclerosis-related forms.Over a 3-yr period, from 1998 to 2001, 243 subjects with pulmonary lymphangioleiomyomatosis were enrolled into a national registry; 13 subjects who had already undergone lung transplantation were excluded for the purposes of this report.All 230 subjects were women, aged 18 to 76 yr (mean +/- SE, 44.5 +/- 0.65 yr). The average age at onset of symptoms was 38.9 +/- 0.73 yr and at diagnosis was 41.0 +/- 0.65 yr. Tuberous sclerosis complex was present in 14.8% of subjects. Pulmonary manifestations, most commonly spontaneous pneumothorax, were the primary events leading to the diagnosis in 86.5% of cases. Nearly 55% of the subjects were being treated with a progesterone derivative. An obstructive pattern on pulmonary function testing was observed in 57.3% of the subjects, whereas 33.9% had normal spirometric results. Women with tuberous sclerosis-related lymphangioleiomyomatosis were younger and had less impaired lung function compared with those with the sporadic form.The age range of women afflicted with pulmonary lymphangioleiomyomatosis is broader than previously appreciated and the degree of pulmonary function can be quite variable, with one-third of subjects having normal spirometry at enrollment into this registry.

    View details for DOI 10.1164/rccm.200409-1298OC

    View details for Web of Science ID 000234520400017

    View details for PubMedID 16210669

    View details for PubMedCentralID PMC2662978

  • A multiparameter wearable physiologic monitoring system for space and terrestrial applications International Workshop on New Generation of Smart Wearable Health Systems and Applications Mundt, C. W., Montgomery, K. N., Udoh, U. E., Barker, V. N., Thonier, G. C., Tellier, A. M., Ricks, R. D., Darling, R. B., Cagle, Y. D., Cabrol, N. A., Ruoss, S. J., Swain, J. L., Hines, J. W., Kovacs, G. T. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2005: 382–91


    A novel, unobtrusive and wearable, multiparameter ambulatory physiologic monitoring system for space and terrestrial applications, termed LifeGuard, is presented. The core element is a wearable monitor, the crew physiologic observation device (CPOD), that provides the capability to continuously record two standard electrocardiogram leads, respiration rate via impedance plethysmography, heart rate, hemoglobin oxygen saturation, ambient or body temperature, three axes of acceleration, and blood pressure. These parameters can be digitally recorded with high fidelity over a 9-h period with precise time stamps and user-defined event markers. Data can be continuously streamed to a base station using a built-in Bluetooth RF link or stored in 32 MB of on-board flash memory and downloaded to a personal computer using a serial port. The device is powered by two AAA batteries. The design, laboratory, and field testing of the wearable monitors are described.

    View details for DOI 10.1109/TITB.2005.854509

    View details for Web of Science ID 000231747500010

    View details for PubMedID 16167692

  • Smoking cessation: techniques and potential benefits. Thoracic surgery clinics Ziedalski, T. M., Ruoss, S. J. 2005; 15 (2): 189-194


    Smokers have a significantly greater risk of complications during and after operations. Cigarette smoke has significant effects on cardiac function, circulation, and respiratory function. Preliminary studies suggest that smoking cessation for a minimum of 6 to 8 weeks before surgery is required to reduce the perioperative and postoperative risks of smoking. Smoking cessation programs that employ advice, support groups, nicotine replacement therapy, or some anti-depressants have been used successfully in many situations and should be used to discourage smoking preoperatively. Further research is needed, however, to clarify the best approach to smoking cessation for surgical patients.

    View details for PubMedID 15999516

  • Recurrence of pulmonary intravascular bronchoalveolar tumor with mediastinal metastasis 20 years later CHEST 2004 Conference Chen, T. M., Donington, J., Mak, G., Ruoss, S., Upadhyay, D. AMER COLL CHEST PHYSICIANS. 2004: 961S–961S
  • A dose-response study of acetazolamide for acute mountain sickness prophylaxis in vacationing tourists at 12,000 feet (3630 m) HIGH ALTITUDE MEDICINE & BIOLOGY Carlsten, C., Swenson, E. R., Ruoss, S. 2004; 5 (1): 33-39


    The study objective was to determine whether acetazolamide is effective in prophylaxis of acute mountain sickness (AMS) at moderate altitude in ambulatory travelers not undergoing vigorous exercise. Volunteers vacationing in La Paz, Bolivia (3630 m), immediately after arrival from sea level were studied. The design was a double-blind, randomized trial of two doses of acetazolamide (125 mg twice daily, 250 mg twice daily) versus placebo twice daily over a 24-h period. The main outcome measure was AMS score and score trend, using the Lake Louise consensus questionnaire. Nine of 32 subjects (28%) had symptom scoring diagnostic of AMS at 0 h. At 0 and 24 h (respectively), the mean Lake Louise scores were 1.73 and 1.09 for the 11 subjects receiving placebo, 1.45 and 1.36 for the 11 subjects receiving the 125-mg dose, and 2.7 and 0.6 for the 11 subjects receiving the 250-mg dose. The absolute change in these mean scores was not significant for placebo (p = 0.21) or the 125-mg dose (p = 0.88), but was significant for the 250-mg dose (p = 0.008). A comparison of a difference in decline in average AMS score over time showed a statistically significant decline for the 250-mg dosing group versus placebo (p = 0.002). The 250-mg dose of acetazolamide twice daily (but not 125 mg twice daily) was effective in inducing a significant decline in AMS symptoms over the 24-h period after arrival to 3630 m. These results suggest that the dosing of acetazolamide for AMS prevention in nonmountaineering tourists at altitudes below 3700 m should not be lowered below 250 mg twice daily.

    View details for Web of Science ID 000220869500005

    View details for PubMedID 15072715

  • Acute respiratory failure with thrombocytopenia in a 47-year-old woman after hiking in the Sierras CHEST Sankaranarayanan, V., Sharp, V., Ruoss, S. 2003; 124 (2): 754-757

    View details for Web of Science ID 000184801000051

    View details for PubMedID 12907570

  • Cellulose granulomatosis presenting as centrilobular nodules: CT and histologic findings AMERICAN JOURNAL OF ROENTGENOLOGY Bendeck, S. E., Leung, A. N., Berry, G. J., Daniel, D., Ruoss, S. J. 2001; 177 (5): 1151-1153

    View details for Web of Science ID 000171732700034

    View details for PubMedID 11641191

  • Nasal-pulmonary relations in allergic fungal sinusitis and allergic bronchopulmonary aspergillosis CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY Leonard, C. T., Berry, G. J., Ruoss, S. J. 2001; 21 (1): 5-15

    View details for Web of Science ID 000169702700002

    View details for PubMedID 11471340

  • Paclitaxel-induced hypersensitivity pneumonitis: radiographic and CT findings. AJR. American journal of roentgenology Wong, P., Leung, A. N., Berry, G. J., Atkins, K. A., Montoya, J. G., Ruoss, S. J., Stockdale, F. E. 2001; 176 (3): 718-720

    View details for PubMedID 11222212

  • Case report - Paclitaxel-induced hypersensitivity pneumonitis: Radiographic and CT findings AMERICAN JOURNAL OF ROENTGENOLOGY Wong, P., Leung, A. N., Berry, G. J., Atkins, K. A., Montoya, J. G., Ruoss, S. J., Stockdale, F. E. 2001; 176 (3): 718-720
  • Plasma vascular endothelial growth factor in acute mountain sickness CHEST Maloney, J., Wang, D., Duncan, T., Voelkel, N., Ruoss, S. 2000; 118 (1): 47-52


    To investigate the hypothesis that an increase in circulating vascular endothelial growth factor (VEGF) occurs in mountaineers at high altitude, particularly in association with acute mountain sickness (AMS) and/or low hemoglobin oxygen saturation.: Collection of medical histories, AMS scores, plasma samples, and arterial oxygen saturation (SaO(2)) measurements from mountaineers at 1,500 feet (sea level) and at 14,200 feet.Mount McKinley ("Denali"), AK.Sixty-six mountaineers.None.Plasma VEGF at 14,200 feet was not increased in any group. In fact, plasma VEGF was significantly lower in subjects who did not develop AMS (53 +/- 7.9 pg/mL; mean +/- SEM; n = 47) compared to control subjects at sea level (98.4 +/- 14.3 pg/mL; n = 7; p = 0.005). Plasma VEGF at 14, 200 feet for subjects with AMS (62 +/- 12 pg/mL; n = 15) did not differ significantly from subjects at 14,200 feet without AMS, or from control subjects at sea level. Of a small number of subjects with paired specimens at sea level and at base camp (n = 5), subjects who exhibited a decrease in plasma VEGF at 14,200 feet were those who did not develop AMS. Neither SaO(2), prior AMS, AMS symptom scores, or acetazolamide use were correlated with plasma VEGF.Subjects at high altitude who do not develop AMS have lower plasma VEGF levels compared to control subjects at sea level. Plasma VEGF at high altitude is not elevated in association with AMS or hypoxia. Sustained plasma VEGF at altitude may reflect a phenotype more susceptible to AMS.

    View details for Web of Science ID 000088284800014

    View details for PubMedID 10893358

  • Thoracic lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Faul, J. L., Berry, G. J., Colby, T. V., Ruoss, S. J., Walter, M. B., Rosen, G. D., Raffin, T. A. 2000; 161 (3): 1037-1046

    View details for Web of Science ID 000085996400058

    View details for PubMedID 10712360

  • Inhalational anthrax - Epidemiology, diagnosis, and management CHEST Shafazand, S., Doyle, R., Ruoss, S., Weinacker, A., Raffin, T. A. 1999; 116 (5): 1369-1376


    Anthrax, a disease of great historical interest, is once again making headlines as an agent of biological warfare. Bacillus anthracis, a rod-shaped, spore-forming bacterium, primarily infects herbivores. Humans can acquire anthrax by agricultural or industrial exposure to infected animals or animal products. More recently, the potential for intentional release of anthrax spores in the environment has caused much concern. The common clinical manifestations of anthrax are cutaneous disease, pulmonary disease from inhalation of anthrax spores, and GI disease. The course of inhalational anthrax is dramatic, from the insidious onset of nonspecific influenza-like symptoms to severe dyspnea, hypotension, and hemorrhage within days of exposure. A rapid decline, culminating in septic shock, respiratory distress, and death within 24 h is not uncommon. The high mortality seen in inhalational anthrax is in part due to delays in diagnosis. Classic findings on the chest radiograph include widening of the mediastinum as well as pleural effusions. Pneumonia is less common; key pathologic manifestations include severe hemorrhagic mediastinitis, diffuse hemorrhagic lymphadenitis, and edema. Diagnosis requires a high index of suspicion. Treatment involves supportive care in an intensive care facility and high doses of penicillin. Resistance to third-generation cephalosporins has been noted. Vaccines are currently available and have been shown to be effective against aerosolized exposure in animal studies.

    View details for Web of Science ID 000083723900041

    View details for PubMedID 10559102

  • Tick-borne pulmonary disease - Update on diagnosis and management CHEST Faul, J. L., Doyle, R. L., Kao, P. N., Ruoss, S. J. 1999; 116 (1): 222-230


    Ticks are capable of transmitting viruses, bacteria, protozoa, and rickettsiae to man. Several of these tick-borne pathogens can lead to pulmonary disease. Characteristic clinical features, such as erythema migrans in Lyme disease, or spotted rash in a spotted fever group disease, may serve as important diagnostic clues. Successful management of tick-borne diseases depends on a high index of suspicion and recognition of their clinical features. Patients at risk for tick bites may be coinfected with two or more tick-borne pathogens. A Lyme vaccine has recently become available for use in the United States. Disease prevention depends on the avoidance of tick bites. When patients present with respiratory symptoms and a history of a recent tick bite or a characteristic skin rash, a differential diagnosis of a tick-borne pulmonary disease should be considered. Early diagnosis and appropriate antibiotic therapy for these disorders lead to greatly improved outcomes.

    View details for Web of Science ID 000081513200037

    View details for PubMedID 10424529

  • Mycobacterium avium-intracellulare pulmonary infection in HIV-negative patients without preexisting lung disease - Diagnostic and management limitations CHEST Huang, J. H., Kao, P. N., Adi, V., Ruoss, S. J. 1999; 115 (4): 1033-1040


    To review the experience of an outpatient pulmonary clinic with Mycobacterium avium-intracellulare (MAI) pulmonary disease in the HIV-negative population without preexisting lung disease.Retrospective clinical series.University medical center.The clinic charts of all patients who fulfilled the current American Thoracic Society criteria for MAI pulmonary infection and who had no preexisting lung disease or immunosuppression were reviewed.Of 31 patients identified, 94% were female, 90% were white, and the median age at diagnosis was 63 years. The median time interval from symptom onset to diagnosis was 10 months. Bronchiectasis or small nodules without predilection for any lobe was found in 93%. Bronchoscopy or open lung biopsy for diagnosis was required in 45% because of nondiagnostic sputum cultures. At > or = 12 months, 50% failed therapy, 86% continued to be symptomatic, and 58% did not tolerate their initial multidrug regimen.These results emphasize the observed chronic nature of MAI pulmonary disease in this population, both before diagnosis and despite therapy. The sensitivity of sputum culture in this population is low, so an aggressive diagnostic approach, including bronchoscopy, should be considered if sputum cultures are negative. Current treatments are suboptimal because of poor drug tolerance and significant failure rates. Last, the preponderance of disease in older white women argues for a genetic or acquired immune deficiency to explain disease susceptibility.

    View details for PubMedID 10208205

  • Diaphragmatic paralysis due to Lyme disease EUROPEAN RESPIRATORY JOURNAL Faul, J. L., Ruoss, S., Doyle, R. L., Kao, P. N. 1999; 13 (3): 700-702


    Lyme disease is a tick-borne spirochaete infection which, in a proportion of patients, can lead to neuropathy. This article describes a case of diaphragmatic paralysis due to Lyme disease. A 39-yr-old male presented to the hospital because of an acute left facial palsy. Six weeks prior to admission he had developed a circular rash on his left flank during a camping holiday. He also complained of shortness of breath and arthralgia for 1 week. His chest radiograph demonstrated a raised right hemi-diaphragm. Diaphragmatic paralysis was confirmed by fluoroscopy (a positive sniff test). Serology revealed evidence of recent infection by Borrelia burgdorferi. On the basis of the patient's clinical presentation, a recent history of erythema migrans, and positive Lyme serology, a diagnosis of neuroborreliosis was made. He received oral doxycycline therapy (200 mg x day(-1)) for three weeks. Facial and diaphragmatic palsies resolved within eight weeks. On the basis of this case, a diagnosis of Lyme disease should be considered in patients from endemic regions with otherwise unexplained phrenic nerve palsy.

    View details for Web of Science ID 000079849000041

    View details for PubMedID 10232450

  • Analyses of the NRAMP1 and IFN-gamma R1 genes in women with Mycobacterium avium-intracellulare pulmonary disease AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Huang, J. H., Oefner, P. J., Adi, V., Ratnam, K., Ruoss, S. J., Trako, E., Kao, P. N. 1998; 157 (2): 377-381


    Mycobacterium avium-intracellulare (MAI) pulmonary disease causes substantial morbidity in a population of older, HIV-negative women without preexisting lung disease. The cause for disease susceptibility in these patients is unknown, although their relative phenotypic homogeneity suggests the existence of a common, subtle immune deficiency. An investigation was undertaken to determine if these patients have a defect in their natural resistance-associated macrophage protein (NRAMP1) or interferon gamma receptor 1 (IFN-gammaR1) genes. A point mutation in murine nramp, an autosomal recessive gene controlling resistance to intracellular organisms, correlates with overwhelming Mycobacterium bovis infection in mice. The corresponding region in human NRAMP1, two coding polymorphisms and one promoter NRAMP1 polymorphism, as well as two IFN-gammaR1 polymorphisms, were analyzed to determine if an allele was present to correlate with disease. Genomic DNA was purified from eight women with MAI pulmonary disease and four controls. Regions of interest were amplified by PCR; three sites were analyzed by restriction fragment length polymorphisms, and three were analyzed using denaturing high-performance liquid chromatography. The NRAMP1 promoter polymorphism of 18 additional random controls was analyzed by microsatellite sizing. No allelism was found in NRAMP1 corresponding to the murine mutation, or in the two coding regions. In the NRAMP1 promoter microsatellite, 3 of 8 patients were heterozygous for a dinucleotide sequence insertion, as were 10 of 22 controls. None of the patients had either of the two known IFN-gammaR1 mutations. In conclusion, in women with MAI pulmonary disease, there is no evidence for a genetic defect in NRAMP1 or IFN-gammaR1 to correlate with disease.

    View details for PubMedID 9476846

  • Lymphangioleiomyomatosis: New insights AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Kalassian, K. G., Doyle, R., Kao, P., Ruoss, S., Raffin, T. A. 1997; 155 (4): 1183-1186

    View details for Web of Science ID A1997WR65700002

    View details for PubMedID 9105053

  • Pulmonary capillaritis and alveolar hemorrhage - Update on diagnosis and management CHEST Green, R. J., Ruoss, S. J., KRAFT, S. A., Berry, G. J., Raffin, T. A. 1996; 110 (5): 1305-1316


    Pulmonary vascular inflammatory disorders may involve all components of the pulmonary vasculature, including capillaries. The principal histopathologic features of pulmonary capillaritis include capillary wall necrosis with infiltration by neutrophils, interstitial erythrocytes, and/or hemosiderin, and interalveolar septal capillary occlusion by fibrin thrombi. Immune complex deposition is variably present. Patients often present clinically with diffuse alveolar hemorrhage, which is characterized by dyspnea and hemoptysis; diffuse, bilateral, alveolar infiltrates on chest radiograph; and anemia. Pulmonary capillaritis has been reported with variable frequency and severity as a manifestation of Wegener's granulomatosis, microscopic polyarteritis, systemic lupus erythematosus, Goodpasture's syndrome, idiopathic pulmonary renal syndrome, Behçet's syndrome, Henoch-Schönlein purpura, IgA nephropathy, antiphospholipid syndrome, progressive systemic sclerosis, and diphenylhydantoin use. In addition to history, physical examination, and routine laboratory studies, certain ancillary laboratory tests, such as antineutrophil cytoplasmic antibodies, antinuclear antibodies, and antiglomerular basement membrane antibodies, may help diagnose an underlying disease. Diagnosis of pulmonary capillaritis can be made by fiberoptic bronchoscopy with transbronchial biopsy, but thoracoscopic biopsy is often employed. Since many disorders can result in pulmonary capillaritis with diffuse alveolar hemorrhage, it is crucial for clinicians and pathologists to work together when attempting to identify an underlying disease. Therapy depends on the disorder that gave rise to the pulmonary capillaritis and usually includes corticosteroids and cyclophosphamide or azathioprine. Since most diseases that result in pulmonary capillaritis are treated with immunosuppression, infection must be excluded aggressively.

    View details for Web of Science ID A1996VR83500037

    View details for PubMedID 8915239



    We report the existence of a new Chinese hamster thrombin receptor allele, characterized by an in-frame insertion of three nucleotides at position 250 of the published sequence. As a consequence, an additional proline is inserted into a proline-rich region of the extracellular amino-terminal domain of the receptor. A corresponding proline at this position is also found in the rat thrombin receptor. A silent base-pair change is found in the cytoplasmic tail of the receptor gene. Single-strand conformation polymorphism and sequence analysis indicate this new receptor allele is present in several cell lines derived from different individual Chinese hamsters. Embryonic CHEF IIC9 cells and primary culture cells are homozygous for this new allele. In contrast, the CCL39 lung fibroblast cell line is heterozygous for both the new and old alleles. Both alleles are transcribed into mRNA and code for functional receptors. Given the allelic distribution and sequence alignment with thrombin receptors from other species, we propose that the new sequence represents the actual predominant allele in Chinese hamster.

    View details for PubMedID 7488069

  • Mast Cells, Basophils and Eosinophils in the Evolution of Pulmonary Fibrosis Pulmonary Fibrosis (Lung Biology in Health and Disease Series). SH Phan and R Thrall, editors. Marcel Dekker, Inc., New York Ruoss SJ, Caughey GH 1995