Laboratory of Rare Lung Diseases

Information for Doctors

Lymphangioleiomyomatosis (LAM) 

A Safety Study for Women with Sporadic or TS-associated LAM.

Sponsor: LAM Foundation:Investigator Initiated.

The purpose of this research study is to see if simvastatin can be taken safely in patients with either LAM or TSC, who are already being treated with everolimus or sirolimus. This is the first step in looking at simvastatin as a drug that may help patients, by impacting the growth and survival of cells that make up the lung lesions that cause problems in LAM and TSC patients. The study also seeks to learn more about how simvastatin works, when given to patients being treated with everolimus or sirolimus, and to evaluate the safety and any potential benefit to patients taking this 2-drug combination. Eligible patients will be assigned to receive 20 mg of simvastatin once daily for a period of two months. If tolerated, the dosage of simvastatin will be advanced to 40 mg once daily in months 3 and 4.

Primary Outcome Measures:
• Safety of simvastatin in the treatment of LAM-S and LAM-TS patients on a stable (for at least 3 months) dose of sirolimus or everolimus.
Secondary Outcome Measures:
• FEV1, FVC, DLCO, VEGF-D, and QOL; signs of clinical benefit.  Pulmonary measures (FEV1, FVC, DLCO), VEGF-D, and QOL; signs of clinical benefit.


The Effects of Ozone on Prostaglandin Secretion and Pulmonary Function Tests in Mild Persistent and Intermittent Asthmatics.

Sponsor: Investigator Initiated.

The purpose of this study is to investigate whether ozone induces eicosanoid prostaglandin secretion that is associated with a decreased FEV1 in mild persistent and intermittent asthmatics. The subjects will be randomized and exposed to either ozone at a known concentration, or forced air in an ozone chamber while exercising. They will be tested for urinary HETE levels and prostaglandin metabolites immediately post exposure and within 24 hours after exposure. They will also receive exhaled NO testing, spirometry and induced sputum testing. The entire test will be repeated 7-10 days later with the alternate arm (i.e. ozone/forced air – whichever wasn't previously tested.). This pilot study will determine the earliest events that predict subsequent inflammation in the airways of subjects with asthma.

This will be a pilot, single site, blinded, double arm, exploratory study that will collect urinary samples of inflammatory metabolites as well as airway secretions and blood from asthmatic and healthy subjects after they have been exposed to ozone and forced air in a controlled ozone chamber. 

There will be five visits – the initial screening visit ( visit 1) followed by the controlled chamber visit (visit 2) and a follow up visit within 24 hours of  the second visit (visit 3). Visits 4 and 5 will occur within 14 days of visit 2 and will mimic visits 2 and 3 except that the alternate arm of ozone/forced air will be given in the chamber.

A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy and Safety of Grass (Phleum pratense) Sublingual Tablet (SCH 697243) in Subjects Between 5 and 65 Years of Age, with a History of Grass Pollen-Induced Rhinoconjunctivitis, With or Without Asthma

Sponsor: Merck

The primary objective of this study is to evaluate the efficacy of grass sublingual tablet (SCH 697243) versus placebo in the treatment of grass pollen-induced rhinoconjunctivitis based on the combined (sum of) rhinoconjunctivitis daily symptom score (DSS) and rhinoconjunctivitis daily medication score (DMS), also called total combined score (TCS), averaged over the entire grass pollen season (GPS).

The safety objective is to evaluate the safety and tolerability of SCH 697243 when administered sublingually, once daily, to subjects with a history of grass pollen-inducted rhinoconjunctivitis, with or without asthma.

Subject participation will vary according to the time of screening; however, the maximum participation will be for up to 15 months from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of up to 8 months, each subject will begin receiving assigned treatment at least 12 weeks prior to the start of GPS, and throughout the entire 2012 GPS season. Regardless of regional differences in GPS, the treatment phase of this study will end no later than 31 JUL 2012. Each subject will receive a telephone call to evaluate safety 7 days after their last dose of study drug.

Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma

Sponsor: Boston Scientific Corporation

The objective of this study is to evaluate durability of treatment effect and to continue to evaluate the short-term and longer-term safety profile of the Alair System in the United States in the intended use population (patients 18 years and older with severe persistent asthma) following FDA approval. Durability of the treatment effect will be evaluated by comparing the proportion of subjects who experience severe exacerbations during the first year after Alair treatment with the proportion of subjects who experience severe exacerbations during subsequent 12-month periods out to 5 years. Favorable upper 95% confidence limits of the difference in proportion of subjects experiencing severe exacerbations between the subsequent years and the first year will be used to infer a durable treatment effect.

This is a multicenter, open-label, single arm study. The study population consists of subjects with severe asthma who are still symptomatic despite being managed on conventional state-of-the-art therapy of high doses of inhaled corticosteroids (ICS - doses ≥ 1,000 μg per day beclomethasone or equivalent) and long-acting β2 -agonists (LABA - doses of  ≥ 100 μg per day salmeterol or equivalent).

Efficacy and Biomarker Discovery of Vitamin D3 in the Management of Moderate and Severe Asthma

Sponsor: Investigator Initiated

This is a double-blind, randomized, placebo controlled, trial of the efficacy and safety of 2,000 IU daily, 4,000 IU daily and 400 IU daily vitamin D3 in modulating lung-specific biomarkers. Subject participation will last approximately 16 weeks and will include a screening visit, baseline visit, four monthly visits and telephone calls every two weeks.

The primary endpoint will be a percent change in lung-specific biomarkers that include CYP24A1, fractalkine, cathelicidin and IL-10.

Subjects will be randomly assigned to one of three treatment groups:

  • 4,000 IU daily vitamin D3
  • 2,000 IU daily vitamin D3
  • 400 IU daily vitamin D3 (control group)

After the screening visit and a four-week run-in period demonstrating disease stability and management, subjects will obtain a baseline visit to characterize basal levels of biomarkers and pulmonary function. After randomization, the patient will be followed by monthly clinic visits and telephone calls every two weeks.


A Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of MEDI-563 in Subjects with Moderate-to-Severe Chronic Obstructive Pulmonary Disease and Sputum Eosinophilia

Sponsor: MedImmune

This is a Phase 2a, randomized, double-blind, placebo-controlled, multicenter study evaluating the effect of multiple SC doses of MEDI-563 on the rate of moderate-to-severe AECOPD in adult subjects with moderate-to severe COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD; GOLD, 2009).

Eligible subjects will have a documented history of AECOPD within 2 to 12 months prior to Day 1 and a sputum eosinophil count of ≥ 3.0% within 12 months prior to, or at screening.
Subjects will be screened between Day-56 and Day-29.

Prior to randomization, all subjects will undergo a 28- day run-in period (Day -28 to Day -1), during which their current inhaled corticosteroids and/or long-acting β-agonist will be replaced with Symbicort® (budesonide/formoterol fumarate) 160/4.5 μg/delivered dose: 2 inhalations twice daily if FEV1 is < 50% predicted or Spiriva® (tiotropium bromide monohydrate) 18μg/inhalation once daily if 50% ≤ FEV1 < 80% predicted. The subjects will be provided with a short-acting β2-agonist for symptom relief during the study (albuterol sulfate, Ventolin® HFA). Subjects who remain clinically stable during the 28-day run-in period and meet eligibility criteria will continue the maintenance treatment with Symbicort® or Spiriva® and may be randomized into the study to receive investigational product as an add-on therapy for 48 weeks.

Approximately 90 subjects from multiple sites will be randomized in a 1:1 ratio to receive either 100 mg SC MEDI-563 or placebo. Investigational product (MEDI-563 or placebo) will be administered subcutaneously in an outpatient setting every 28 days for the first 3 doses and then every 56 days for the next 5 doses up to Day 337 (total 8 doses). Subjects will be followed for a total of 32 weeks (to Day 561). Post Day 561, subjects will continue until peripheral blood eosinophil counts return to 50 cells/μL or 20%
of baseline.

Epigenetic Signatures of Airway Inflammation After Oxidative Stress in COPD Subjects

Sponsor: Investigator Initiated

This is an exploratory cross-over study of sputum biomarkers of inflammation associated with epigenetic analyses from COPD subjects and healthy smokers who have been exposed to ozone. The purpose of this study is to investigate the epigenetic signature of sputum-derived neutrophils and macrophages in subjects with COPD and healthy smokers who are exposed to ozone. Subjects will be randomized and exposed to either ozone at 200 parts per billion (0.2 ppm) or filtered air while exercising. Induced sputum will be performed prior to and within 24 hours after exposure. All subjects will be crossed over from forced air to ozone exposure in a randomized manner. Subjects will also receive spirometry and dyspnea assessment scores in addition to traditional COPD clinical measures. The entire testing will be repeated 14-21 days after the last exposure. In addition to the characterization of airway inflammation induced by ozone, the effects of steroids in altering the epigenetic signatures will also be studied. Airway inflammation will be characterized by sputum differential cell counts, chemokine/cytokine levels of TNF, IL-1β, IP-10, IL-6, fractalkine, IL-8 and innate immune molecules such as surfactant protein D. Additionally, eicosanoids (20-HETE) and prostaglandins will be characterized in sputum derived from challenged COPD subjects. Correlations of airway inflammation with systemic inflammatory biomarkers (serum TNF, CRP, IL-6 and fibrinogen levels) will also be performed. Of the 30 patients recruited for this study, 10 will be inhaled corticosteroid naïve and compared with the 10 COPD patients on a stable dose of inhaled corticosteroids and long-acting bronchodilators and 10 subjects will have a 10 pack year smoking history with no evidence of COPD (ie “healthy”). All COPD patients will receive inhaled long-acting muscarinic antagonists as baseline therapy. Since the subjects will be age-, gender- and disease severity-matched, the contribution of steroids in modifying ozone-induced DNA methylation and epigenetic signatures will be assessed. Finally, macrophages and neutrophils obtained from the induced sputum will also be studied ex vivo with regard to cell activation and migration in the presence and absence of dexamethasone and p38 mitogen-activated protein kinase inhibitors (p38 MAPKi).

Collectively, these studies will establish a novel platform to investigate oxidative stress-induced airway inflammation as measured by epigenetic signatures, DNA methylation and airway inflammatory biomarkers in induced sputum of subjects with COPD and healthy smokers.

A Cross-Sectional Study of Surfactant Protein D (SP-D) as a Modulator of Lung Inflammation and COPD Pathogenesis

Sponsor: NIH

Cross-sectional study of SP-D levels and quaternary structure in bronchoalveolar lavage fluid from COPD subjects and healthy controls adjusting for the effects of cigarette smoke. SP-D levels and structure will be correlated with inflammatory cell counts and cytokine/chemokine levels in the lavage fluid. In a substudy using a proof-of-concept trial design, COPD subjects not on inhaled corticosteroids or long-acting beta agonsists will undergo collection of bronchoalveolar lavage fluid both before and after a two-week course of treatment with fluticasone/salmeterol (Advair 250/50 mcg), which is FDA-approved for treatment of COPD.

Our preliminary data indicate that subjects with COPD and subjects who smoke have lower SP-D levels in the lung than healthy subjects or non-smokers, respectively. We hope to confirm and elucidate this finding in a larger group to meet the following objectives: (1) To define the association between the total level and/or quaternary structure of SP-D and COPD, controlling for smoking status. (2) To determine the relationship between the total level and/or quaternary structure of SP-D and airway inflammation as measured by cell counts and inflammatory cytokines in BALF and sputum. (3) To determine whether levels of SP-D, its quaternary structure, and inflammatory cytokine expression in BALF are altered by initiation of inhaled corticosteroid/long-acting beta agonist (ICS/LABA) treatment. 

For COPD subjects: age ≥40; ≥10 pack-years of tobacco; FEV1/FVC <0.70; FEV1 <80% predicted. For healthy subjects: age ≥ 40; no evidence of obstruction or restriction on spirometry; smokers and non-smokers included.


Sponsor: NIH

We propose the formation of a longitudinal cohort of patients with asthma and COPD seen at the Penn Lung Center outpatient practices as well as asthma, COPD, and healthy control subjects seen at the Airways Biology Initiative (ABI) clinical research unit in order to provide a centralized registry of potential research subjects, and where applicable, their biological specimens. The Penn Lung Center outpatient practices include four clinical sites:  the Pulmonary Clinic and the Transplant Clinic at the Hospital of the University of Pennsylvania and the Pulmonary and Allergy/Asthma Clinics at Presbyterian Hospital. Patients seen at these four clinical sites with confirmed diagnoses of asthma or COPD, as well as research subjects seen at the ABI, will be approached to participate while receiving their usual care. For patients who consent to participate as subjects, demographic, clinical, and brief questionnaire data will be collected at the initial registry enrollment visit and during follow-up visits subsequently scheduled as part of their routine care. Subjects will also have the option to consent to donate biological specimens for research, principally blood for genetic and biomarker analysis. Data will be entered into a centralized, secure database that may be accessed by investigators for the purposes of research with permission of a data coordinating committee. The target accrual of subjects is approximately 250 subjects per year for a total cohort of 1250 subjects over the next 5 years.


The proposed cohort registry is designed to address 4 specific aims:

  1. To allow the demographic and clinical characterization of subjects with asthma and COPD as well as healthy control subjects for purposes of identifying subpopulations desirable for various research protocols.
  2. To allow periodic review and descriptive reporting of the demographic and clinical characteristics of subjects with asthma and COPD seen at the Penn Lung Center practices, both to aid in the design of future studies and to identify important underrepresented subpopulations to be recruited for future research.
  3. To facilitate contact with asthma and COPD subjects potentially willing to participate in future research studies.
  4. To catalogue biological specimens, principally (but not exclusively) blood and urine samples, obtained from subjects with well-characterized disease for use in basic science and translational research projects.


Microbiome Study

This is a non-interventional cohort study with single time point cross sectional comparisons, and longitudinal analyses, with the primary study aims of evaluating how the immune deficiency associated with HIV infection influences the microbiome of the upper and lower respiratory tract and lung function, how COPD influences the microbiome of the upper and lower respiratory tract, how smoking influences the microbiome of the upper and lower respiratory tract, and the relationship between the microbiome of the upper respiratory tract and the gastrointestinal tract.  

Visits will include 3 visits within 30 days (Screening/Baseline, chest CT, bronchoscopy) then annually for the next 3 years.


  • HIV+ CD4+ ≥400 and will have decided together with their primary care providers to not begin ART.  non-smokers and smokers.  
  • HIV+ CD4+ counts of 200-400 non-smokers. 
  • HIV+ on ART with HIV viral loads suppressed below detectable levels. 
  • HIV+ COPD/emphysema (moderate stage 2).
  • HIV+ no lung disease and will be matched to the above group by age, race, gender, and CD4+ count.
  • HIV- COPD/Emphysema (moderate-stage 2)
  • HIV- no COPD/healthy