Clinical Focus


  • Pediatric Pulmonology

Academic Appointments


Professional Education


  • Board Certification: American Board of Pediatrics, Pediatric Pulmonology (1986)
  • Board Certification: American Board of Pediatrics, Pediatrics (1986)
  • Fellowship: St Christophers Hospital Pediatric Pulmonology (1986) PA
  • Residency: Children's Hospital of Oakland (1983) CA
  • Internship: University of Toledo College of Medicine and Life Sciences Registrar (1980) OH
  • Medical Education: University of Toledo College of Medicine and Life Sciences Registrar (1979) OH

All Publications


  • LONGITUDINAL ASSESSMENT OF SWEAT CHLORIDE CONCENTRATION AMONG INFANTS POSITIVE TO CYSTIC FIBROSIS NEWBORN SCREENING (CF NBS) IN CALIFORNIA Zirbes, J. M., Hardy, K., Sudhakar, R., Salinas, D. B., Saeed, M., Marty, K., Milla, C. E. WILEY-BLACKWELL. 2014: 388
  • Novel CFTR Variants Identified during the First 3 Years of Cystic Fibrosis Newborn Screening in California JOURNAL OF MOLECULAR DIAGNOSTICS Prach, L., Koepke, R., Kharrazi, M., Keiles, S., Salinas, D. B., Reyes, M. C., Pian, M., Opsimos, H., Otsuka, K. N., Hardy, K. A., Milla, C. E., Zirbes, J. M., Chipps, B., O'Bra, S., Saeed, M. M., Sudhakar, R., Lehto, S., Nielson, D., Shay, G. F., Seastrand, M., Jhawar, S., Nickerson, B., Landon, C., Thompson, A., Nussbaum, E., Chin, T., Wojtczak, H. 2013; 15 (5): 710-722

    Abstract

    California uses a unique method to screen newborns for cystic fibrosis (CF) that includes gene scanning and DNA sequencing after only one California-40 cystic fibrosis transmembrane conductance regulator (CFTR) panel mutation has been identified in hypertrypsinogenemic specimens. Newborns found by sequencing to have one or more additional mutations or variants (including novel variants) in the CFTR gene are systematically followed, allowing for prospective assessment of the pathogenic potential of these variants. During the first 3 years of screening, 55 novel variants were identified. Six of these novel variants were discovered in five screen-negative participants and three were identified in multiple unrelated participants. Ten novel variants (c.2554_2555insT, p.F1107L, c.-152G>C, p.L323P, p.L32M, c.2883_2886dupGTCA, c.2349_2350insT, p.K114del, c.-602A>T, and c.2822delT) were associated with a CF phenotype (42% of participants were diagnosed at 4 to 25 months of age), whereas 26 were associated with CFTR-related metabolic syndrome to date. Associations with the remaining novel variants were confounded by the presence of other diseases or other mutations in cis or by inadequate follow-up. These findings have implications for how CF newborn screening and follow-up is conducted and will help guide which genotypes should, and which should not, be considered screen positive for CF in California and elsewhere.

    View details for DOI 10.1016/j.jmoldx.2013.05.006

    View details for Web of Science ID 000323870900019

    View details for PubMedID 23810505

  • Long term effects of denufosol tetrasodium in patients with cystic fibrosis JOURNAL OF CYSTIC FIBROSIS Ratjen, F., Durham, T., Navratil, T., Schaberg, A., Accurso, F. J., Wainwright, C., Barnes, M., Moss, R. B. 2012; 11 (6): 539-549

    Abstract

    Denufosol stimulates chloride secretion independent of the chloride channel which is dysfunctional in cystic fibrosis (CF) and therefore has the potential to benefit CF patients regardless of genotype.To assess the efficacy of denufosol in CF patients with mild lung function impairment age 5 years and older.This multicenter, randomized, parallel group double-blind placebo-controlled trial was conducted at 102 CF care centers in Australia, Canada and the United States (NCT00625612) The active group (n=233) received 60 mg denufosol via inhalation three times daily The primary efficacy endpoint was change in FEV(1) in liters from Day 0 to week 48.685 patients were screened for the study and 466 patients (233 in each group) were randomized to study treatment. The adjusted mean change in FEV(1)was 40 mL for denufosol and 32 mL for placebo with a resulting treatment effect of 8 mL (95% CI -0.040, 0.056). The average rate of change in FEV(1) percent of predicted over 0 to 48 weeks was -3.04% for placebo vs. -2.30 for denufosol (a difference of 24% relative to placebo) among all patients. The incidence of pulmonary exacerbation was 26% vs. 21% for the placebo and denufosol groups with no differences in the time to first event. The study treatments were well tolerated and there was no evidence of systemic effects in any safety parameter assessed.In patients with CF treatment with denufosol for 48 weeks did not improve pulmonary function or reduce the incidence of pulmonary exacerbations.

    View details for DOI 10.1016/j.jcf.2012.05.003

    View details for Web of Science ID 000312115900009

    View details for PubMedID 22682898

  • Denufosol Tetrasodium in Patients with Cystic Fibrosis and Normal to Mildly Impaired Lung Function AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Accurso, F. J., Moss, R. B., Wilmott, R. W., Anbar, R. D., Schaberg, A. E., Durham, T. A., Ramsey, B. W. 2011; 183 (5): 627-634

    Abstract

    Intervention for cystic fibrosis lung disease early in its course has the potential to delay or prevent progressive changes that lead to irreversible airflow obstruction. Denufosol is a novel ion channel regulator designed to correct the ion transport defect and increase the overall mucociliary clearance in cystic fibrosis lung disease by increasing chloride secretion, inhibiting sodium absorption, and increasing ciliary beat frequency in the airway epithelium independently of cystic fibrosis transmembrane conductance regulator genotype.To evaluate the efficacy and safety of denufosol in patients with cystic fibrosis who had normal to mildly impaired lung function characteristic of early cystic fibrosis.A total of 352 patients greater than or equal to 5 years old with cystic fibrosis who had FEV(1) greater than or equal to 75% of predicted normal were randomized to receive inhaled denufosol, 60 mg, or placebo three times daily in a Phase 3, randomized, double-blind, placebo-controlled, 24-week trial.Main outcome measures included change in FEV(1) from baseline to Week 24 endpoint and adverse events. Mean change from baseline to Week 24 endpoint in FEV(1) (primary efficacy endpoint) was 0.048 L for denufosol (n = 178) and 0.003 L for placebo (n = 174; P = 0.047). No significant differences between groups were observed for secondary endpoints including exacerbation rate and other measures of lung function. Denufosol was well tolerated with adverse event and growth profiles similar to placebo.Denufosol improved lung function relative to placebo in cystic fibrosis patients with normal to mildly impaired lung function. Clinical trial registered with www.clinicaltrials.gov (NCT00357279).

    View details for DOI 10.1164/rccm.201008-1267OC

    View details for Web of Science ID 000288296000015

    View details for PubMedID 21169471

  • LONGITUDINAL ASSESSMENT OF SWEAT CHLORIDE VALUES IN INFANTS WITH 2 CFTR MUTATIONS IDENTIFIED BY NEWBORN SCREENING Zirbes, J. M., Hardy, K., Kharrazi, M., Milla, C. WILEY-BLACKWELL. 2011: 370–71
  • Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants PEDIATRICS Null, D., Bimle, C., Weisman, L., Johnson, K., Steichen, J., Singh, S., Wang, E., Asztalos, E., Loeffler, A. M., Azimi, P. H., Lieberman, J. M., O'Donnell, N. E., Cooke, R. J., McCormick, K., Koo, W., Hammami, M., Milner, A. D., Gaon, P., Nachman, S., Tarpey, K. P., Sanchez, P. J., Broyles, R. S., Bratcher, D., Ball, M. V., Duda, F. J., DeCuir, P. M., Pollara, B., Nelson, L. S., Balbus, M., Schultz, M. J., Chipps, B. E., Givner, L. B., O'Shea, M., Everard, M., Pfeffer, K., Page, A. J., Dennehy, P. H., Modlin, J., Rhodes, T., DeVincenzo, N., Nickerson, B., Arrieta, A., Boucher, F. D., Keeney, R. E., Young, T. E., Stevens, J. C., Ariagno, R., Adams, M., Polak, M. J., Lynch, S. K., Gerdes, J. S., Kuba, M., Aouthmany, M., Lamar, K., Chang, G. Y., Shelton, M. M., Hadeed, S. K., Vasan, U., Hennessy, A., YOGEV, R., Welliver, R. C., Tristram, D., Albin, C., Jefferson, T. T., Purdy, G. D., Buckner, C. M., Schlessel, J., Sia, C., Tan, B., Sankaran, K., Morley, C. J., White, D. K., Meissner, H. C., Frantz, I., Desai, S. A., Stanley, C. W., Inwood, R., Solecki, L. E., Wald, E., Smail, K., Fox, R. E., Taciak, V., Park, C. L., Vidyasagar, D., Redding, G., Mayock, D. E., Reuman, P. D., Bifano, E. M., Estrada, B., Mancao, M. Y., Hook, B., McDavid, G., Rowen, J. L., Patel, J. A., Robinson, J., Lee, B., Rodriguez, W., Arrobio, J., Hocker, J. R., McConnell, C., Piedimonte, G., Sosenko, I., Patel, B., Shervinski, S., Stobie, P. E., Perea, K., Chartrand, S. A., Wilson, M. C., de Lemos, R., Ramanathan, R., Barnett, B. A., Luber, S. R., Raszka, W. V., Holsclaw, D. S., Klein, D. L., Law, B. J., Balsan, M. J., Douglass, B. H., O'Sullivan, B. P., Spaulding, R., Van Dyke, R. B., Merza, A., Hendley, J. O., Boyle, R. J., Hughes, P. A., Horgan, M. J., Maynard, R. C., Teufert, K., Majure, M., George, J. A., Kuerschner, D. R., Ghai, V., Thomas, D., MacDonald, N., Kovesi, T., Blayney, M., Mani, C. S., San Joaquin, V. H., Roberts, L., Wiznia, A., Rosenberg, M., Karna, P., Murray, D. L., Lenney, W., Clayton, S., Oelberg, D. G., Reininger, M. M., Eppes, S. C., Childs, J. A., Gruber, W. C., Hazinski, T. R., Steinberg, E. A., Lopez, L. C., Elliott, G. R., Groothuis, J. R., Simoes, E. E., Hakim, A., Mimouni, F., Rubin, L., Sood, S. K., Sadiq, H. F., Marshall, T. G., Miller, D., Drayton, M. R., O'Neill, S., Chetcuti, P., Trupp, D. L., Heart, J., Cooper, E. R., Brown, E. R., Chetty, A., Rice, T. B., Rupar, D., Cho, C. T., Leff, R. D., Levine, S. D., Kolls, J. K., Hall, M., Smith, S. L., Schwartz, L., Lemen, R. J., Hall, C. B., Long, C. E., Panitch, H., Kolb, S. M., Colombo, J. L., Judy, C. G., Golembe, B. L., Anderson, J. D., McDonald, J., Mccormack, D., Ruggerie, D. P., Triplett, C., Odom, M. W., Lopez-Cox, G., Sawyer, M. H., Connor, J. D., Fergie, J. E., Purcell, K., Kantak, A. D., Fihe, D. M., Davies, H. D., Mitchell, L., Subramanian, K. N., Smith, Y., St John, E. B., Stolz, J. W., Sheils, C., Cox, F., Foshee, W., Diaz, R., Coonce, S., Keyserling, H. L., Padrick, C. B., Lamprecht, C., Livingston, F. R., Langley, J. M., Weller, P., Cropp, G. J., Sola, A., Kumar, M. L., Lapin, C. D., Carlisle, P., Martz, R., Radetsky, M., Midani, S., Rathore, M. H., Riff, E. J., Shay, G. F., Hogvall, E., Russell, D. W., Thomson, A. H., Lawrey, S. M., Hardy, K., Harvey, K., Turner, R., Cox, E. O., Dana, A., Madan, A., Wallace, J., Stevens, D. C., Asmar, B., Selewski, N. A., Kelly, J., Klerr, T., Spruill, S., Conner, E. M., Carlin, D., Top, F. H. 1998; 102 (3): 531-537
  • PHARMACOKINETICS OF PREDNISONE AND PREDNISOLONE IN CYSTIC-FIBROSIS PATIENTS HALE, V. G., HARDY, K., PALMER, J., TUNTLAND, T., BENET, L. Z. AMER PHARMACEUTICAL ASSN. 1987: S110