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PREVIOUS ISSUES - MARCH 2004
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COURSE DIRECTORS |
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Edward E. Lawson, M.D.
Professor
Department of Pediatrics – Neonatology
The Johns Hopkins University School of Medicine |
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Christoph U. Lehmann, M.D.
Assistant Professor
Department of Pediatrics – Neonatology
The Johns Hopkins University School of Medicine |
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Lawrence M. Nogee, M.D.
Associate Professor
Department of Pediatrics – Neonatology
The Johns Hopkins University School of Medicine |
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Lorraine A. Harbold, R.N., M.S.
The Johns Hopkins Hospital;
NICU Education Coordinator |
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In this issue... Volume 1, Number 7 |
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It is unarguable that the number of patients and the amount of clinical data collected in randomized controlled trials of surfactant preparations over the past 15 years dwarf that of any other clinical arena in neonatology. Many of these trials serve as model templates for the design and execution of future clinical studies. Nonetheless, for all the useful information learned, there are still intriguing questions about surfactant therapy in newborns for which answers are incomplete or controversial.
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Guest Editor of the Month
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Mark L. Hudak, MD
Assistant Dean
Professor and Assistant Chairman
Department of Pediatrics
University of Florida at Jacksonville |
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Guest Faculty Disclosure
Mark L. Hudak, MD
Faculty Disclosure: No relationship with commercial supporters
Unlabelled/Unapproved Uses
Dr Hudak has indicated that the program includes off-label discussions of calfactant and beractant.
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COMMENTARY |
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Many neonatologists still question whether the strategy of early surfactant prophylaxis after premature birth results in better clinical outcomes than a more conservative "rescue" protocol. Although many NICUs have adopted some prophylaxis protocol for the most extremely premature infants (24-26 weeks' gestation), there is no consensus on this issue for infants of more advanced gestations. The largest and most carefully conducted studies with available commercial surfactants support the notion that prophylaxis improves survival through 30 weeks' gestation.
One argument that has been advanced against routine prophylaxis notes that current use of antenatal steroids is now much more frequent (70%-90%) than at the time of the prophylaxis vs. rescue trials (20-30%). Hence, especially among infants of intermediate prematurity, the incidence of severe RDS can be expected to be much lower, thereby allowing a greater clinical buffer regarding the timing of initial surfactant treatment. Inferences drawn from large databases (weaknesses acknowledged) are that the combination of antenatal steroids and prophylactic surfactant improves overall outcome (not solely respiratory) compared to either antenatal steroids or surfactant therapy alone. This inference has solid underpinnings in the experimental animal literature.
Somewhat similarly, a second argument centers on the interim enhancements to conventional ventilation and the increased availability of high frequency ventilation (HFV). However, there is no controlled evidence that refinements in conventional ventilation have reduced mortality nor is there even consensus that early use of HFV is advantageous compared to conventional ventilation. Accordingly, altering surfactant administration strategies on account of the "benefits" associated with these refinements in mechanical ventilatory techniques seems unwarranted.
One small study does suggest a continued benefit to prophylactic vs. rescue surfactant administration in the setting of high frequency oscillation as the primary mode of ventilation (Plavka R et al: see sources for additional information below.) More recently enthusiasts have advocated the practice of deferring prophylactic surfactant in favor of delivery room application of nasal CPAP. The rationale is that immediate inflation of the lungs after birth with stabilization of a normal functional residual capacity via nasal CPAP accomplishes the therapeutic equivalent of exogenous surfactant administration. Randomized controlled trials of this approach compared with prophylactic surfactant followed by ventilation have not been reported.
Perhaps no issue in this field generates more controversy among neonatologists
than the choice of optimal surfactant preparation. The only comparative
study of Survanta (beractant) and Infasurf (calfactant) provides little
independent basis of an efficacy differential (other than a longer duration
of action) for choosing one surfactant over the other. Among infants
in the prophylaxis arm with birth weights less than 600 grams, the Survanta
group showed a surprisingly lower than expected mortality rate, while
the Infasurf group showed mortality as expected in this population.
Clear preclinical differences in efficacy did not translate into perceptibly
improved clinical outcomes. This underpowered trial is just one of many
illustrations of how the significant "noise" introduced by the complex
biology of preterm birth and its aftermath muddies comparative therapeutic
evaluations. It can only be hoped that a future publication of the results
of a large (n > 2000) repeat comparison trial of these two surfactants
(completed by the Pediatrix network in November 2003) will provide more
definitive clinical guidance.
Most centers have expanded indications for surfactant therapy to include
term and near-term infants with meconium aspiration syndrome (MAS) and
pneumonia who are intubated and require significant ventilatory support.
The severity threshold for intervention varies by center and even by
individual neonatologist within a center. Since the publication of the
studies by Findlay et al and Lotze et al, high frequency oscillatory
ventilation and inhaled nitric oxide therapy have become more routine.
The question of whether surfactant replacement confers additional advantage
in this practice setting may never be perfectly answered. Based on the
limited evidence, intervention at a less severe stage of disease and
commitment to two or three total doses once treatment is begun both
appear to be prudent pathways. Further investigation would be necessary
to determine whether surfactant treatment at an earlier stage in the
disease process (e.g., for infants who are on hood oxygen or nCPAP support;
or for infants who are ventilated with OI < 15) is safe and effective.
After an initial positive report, there have been no subsequent follow-up
data concerning lung lavage with dilute surfactant. At this point, the
benefit to risk profile for this novel intervention remains unknown
compared both to control treatment and to standard surfactant replacement
therapy.
Finally, the genetic studies remind us that not all surfactant deficiency conditions are related to immaturity or to inactivation of normal surfactant. In infants with atypical respiratory disease, deficiencies of the hydrophobic surfactants (SP-B and SP-C) should be considered. Because SP-B deficiency has been reported to account for less than 20% of a highly selected cohort of babies with respiratory failure not due to obvious disease conditions, there is little doubt that other genetic bases for surfactant dysfunction will continue to be identified.
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SOURCES FOR ADDITIONAL INFORMATION
Plavka R et al: Early vs. delayed surfactant administration in extremely premature neonates with respiratory distress syndrome ventilated by high-frequency oscillatory ventilation. Intensive Care Med 2002; 28:1483-1490.
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(For non-journal subscribers, an additional fee may apply for full text article)
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Moller JC, Schaible T, Roll C, Schiffman JH et al: Treatment with bovine surfactant in severe acute respiratory distress in children: a randomized multicenter study. Intensive Care Med 2003; 29:437-446
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(For non-journal subscribers, an additional fee may apply for full text article)
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Prophylaxis vs. Rescue Surfactant Treatment for Very Premature Infants
Kendig JW, Notter RH, Cox C, Reubens LJ, Davis JM, Maniscalco WM, Sinkin RA, Bartoletti A, Dweck HS, Horgan MJ, Risemberg H, Phelps DL, Shapiro DL: A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks' gestation. N Engl J Med 1991; 324:865-871
Kattwinkel J, Bloom BT, Delmore P, Davis CL, Farrell E, Friss H, Jung AL, King K, Mueller D: Prophylactic administration of calf lung surfactant extract is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks' gestation. Pediatrics 1993;92:90-98.
Kendig JW, Ryan RM, Sinkin RA, Maniscalco WM, Notter RH, Guillet R, Cox C, Dweck HS, Horgan MJ, Reubens LJ, Risemberg H, Phelps DL: Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial. Pediatrics 1998; 101:1006-1012.
Soll RF: Surfactant therapy: does timing of treatment improve clinical outcome? Neonatal Respiratory Diseases 2002; 12:1-8.
The best available evidence supports the conclusion that early surfactant prophylaxis of very premature infants both improves survival and decreases the severity of RDS and the incidence of air leak complications when compared to a strategy of delaying treatment until threshold respiratory symptoms occur. Note, however, that the gestational age or birth weight breakpoint for this intervention is controversial.
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Multiple controlled studies have sought to determine whether a strategy of early surfactant treatment of very premature infants (prophylaxis) offers clinical advantages over the alternative approach of withholding therapy pending a presumptive diagnosis of surfactant deficiency (rescue). The three clinical trials cited above represent a well-staged investigative approach to the two questions of treatment breakpoint and of timing of initial prophylaxis.
Kendig et al reported that 479 infants with a gestational age of less
than 30 weeks were randomized to receive either a preventilatory dose
of surfactant or to receive treatment when they required either 40%
inspired oxygen or a mean airway pressure of > 7 cm H2O. Fifty-eight
percent of the infants in the latter group eventually received surfactant.
Survival to discharge was significantly higher in the prophylaxis group
compared to the rescue group (88% vs 80%), particularly in the subgroup
of infants at or below 26 weeks' gestation (75% vs. 54%). Infants who
received prophylaxis also had less severe RDS and fewer pneumothoraces;
however, this group developed the same incidence of chronic lung disease
as those infants randomized to the rescue treatment.
Kattwinkel and colleagues extended these observations in a study that
enrolled 1248 infants born between 29 and 32 weeks' gestational age.
Infants were randomized to early prophylaxis (not necessarily preventilatory,
but treated by 5 minutes of age) or treatment at such time as mild RDS
was diagnosed (median age of 1.5 hours). Infants were re-treated when
they required a mean airway pressure ≥ 10 cm H2O and FiO2 ≥ 0.60
to maintain PaO2 > 70 mm Hg. Death (0.5% vs. 1.8%) and death or BPD
(5% vs. 9%) were significantly lower in the prophylaxis compared to
the rescue group. Other respiratory and non-respiratory morbidities
did not differ between the two groups.
In the third trial, also led by Kendig, 651 infants born between 24 to 28 weeks' gestation were randomized to two different surfactant prophylaxis strategies: immediate administration once intubated (preventilatory) vs. treatment after stabilization (postventilatory). In the postventilatory group, survival to discharge was slightly higher and the requirement for supplemental oxygen at 36 weeks' corrected gestational age was slightly lower.
Finally, a meta-analysis by Soll that included 5 additional studies with different study designs concluded that surfactant prophylaxis does improve neonatal outcomes. It was noted that by 1998 that the Vermont-Oxford network centers had not uniformly translated the results of these studies into routine clinical protocols.
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Kendig JW, Notter RH, Cox C, Reubens LJ, Davis JM, Maniscalco WM, Sinkin RA, Bartoletti A, Dweck HS, Horgan MJ, Risemberg H, Phelps DL, Shapiro DL: A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks' gestation. N Engl J Med 1991; 324:865-871
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Kattwinkel J, Bloom BT, Delmore P, Davis CL, Farrell E, Friss H, Jung AL, King K, Mueller D: Prophylactic administration of calf lung surfactant extract is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks' gestation. Pediatrics 1993;92:90-98.
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Kendig JW, Ryan RM, Sinkin RA, Maniscalco WM, Notter RH, Guillet R, Cox C, Dweck HS, Horgan MJ, Reubens LJ, Risemberg H, Phelps DL: Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial. Pediatrics 1998; 101:1006-1012.
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Clinical Comparisons of Commercial Surfactants
Horbar JD, Wright LL, Soll RF et al: A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. J Pediatr 1993;123:757-766.
Vermont-Oxford Neonatal Network: A multicenter randomized trial comparing synthetic surfactant with modified bovine surfactant extract in the treatment of neonatal respiratory distress syndrome. Pediatrics 1996;97:1-6.
Hudak ML, Farrell EE, Rosenberg AA, et al: A multicenter randomized masked comparison of natural vs. synthetic surfactant for the treatment of respiratory distress syndrome. J Pediatr 1996;28:396-406.
Hudak ML, Martin DJ, Egan EA et al: A multicenter randomized masked comparison trial of synthetic surfactant vs. calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome. Pediatrics 1997;100:39-50.
Bloom BT, Kattwinkel J, Hall RT et al: Comparison of Infasurf (calf lung surfactant extract) to Survanta (beractant) in the treatment and prevention of respiratory distress syndrome. Pediatrics 1997;100:31-38.
Animal-based surfactants containing surfactant proteins B and C exhibit significantly greater efficacy in biophysical and animal physiological assays than synthetic surfactants. These preclinical assays have correlated reasonably well with the results of large randomized comparative clinical trials in premature neonates. Each animal-based surfactant preparation has a unique surfactant protein and phospholipid profile that translates into smaller but still substantial differences among these drugs in preclinical efficacy. To date, no study in infants has been adequately powered to determine whether the choice of a particular natural surfactant impacts survival, chronic lung disease, or air leak complications associated with RDS. |
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Exosurf Neonatal (a synthetic surfactant) and Survanta (a modified bovine-derived surfactant) were the first two FDA-approved surfactant preparations. The initial two publications summarize randomized unmasked trials that compared the efficacy and safety of these surfactants in the treatment of established RDS. Horbar et al, in an NIH-sponsored trial (n=617), found that Survanta treatment resulted in a lower average FiO2 and MAP for 72 hours after treatment. Survanta treatment was associated with a non-significant reduction in the incidence of death or BPD (62% vs. 67%) and pneumothorax (9% vs. 13%). The larger (n=1500) Vermont-Oxford network study also noted a significant attenuation of respiratory disease associated with Survanta therapy as well as a decreased incidence of air leak. Survival without BPD was higher in the Survanta treatment group, although these numbers did not reach statistical significance. Despite these rather modest findings, these two studies accelerated an ongoing transition from Exosurf to Survanta as the surfactant of choice in NICUs across the country.
Subsequently, Hudak et al conducted a masked randomized study that compared
Exosurf and Infasurf (an extract of calf lung lavage) for the treatment
of established RDS (n=1033). Infasurf treatment was associated with
significant reductions in the severity of RDS, in the incidences of
pneumothorax and pulmonary interstitial emphysema, and in the duration
of assisted ventilation. The magnitudes of these treatment effects equaled
or exceeded those that had been found in the Exosurf-Survanta trials,
but no significant effect on longer term outcomes such as survival or
BPD was demonstrated. A concomitant study, also led by Hudak, that compared
these two surfactants for the prophylaxis of RDS in infants less than
29 weeks' gestation (n=871), observed significant reductions in the
incidence and severity of RDS, the incidence of air leak, and in RDS-related
mortality -- but no differences in survival to discharge or in the incidence
of BPD.
The comparative trial most germane to current clinical practice is the
Survanta vs. Infasurf trial conducted by Bloom et al. However, the sample
sizes (prophylaxis arm n=374 and rescue arm n=608) were not large enough
to provide definitive guidance about the optimal choice of surfactant
preparation. The intervals between doses were greater for Infasurf and
suggested a longer duration of treatment effect, but mitigation of respiratory
support in the acute phase of RDS was defined only in the treatment
arm. No differences were seen in short- or long-term outcomes, although
mortality was higher in the subgroup of infants with birth weights <
600 grams who received Infasurf prophylaxis (63% vs. 26%, P < .01).
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Horbar JD, Wright LL, Soll RF et al: A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. J Pediatr 1993;123:757-766.
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Vermont-Oxford Neonatal Network: A multicenter randomized trial comparing synthetic surfactant with modifiid bovine surfactant extract in the treatment of neonatal respiratory distress syndrome. Pediatrics 1996;97:1-6.
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Hudak ML, Farrell EE, Rosenberg AA, et al: A multicenter randomized masked comparison of natural vs. synthetic surfactant for the treatment of respiratory distress syndrome. J Pediatr 1996;28:396-406.
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Hudak ML, Martin DJ, Egan EA et al: A multicenter randomized masked comparison trial of synthetic surfactant vs. calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome. Pediatrics 1997;100:39-50.
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Bloom BT, Kattwinkel J, Hall RT et al: Comparison of Infasurf (calf lung surfactant extract) to Survanta (beractant) in the treatment and prevention of respiratory distress syndrome. Pediatrics 1997;100:31-38
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Surfactant Therapy for Non-RDS Respiratory Diseases
Findlay RD, Taeusch HW, Walther FJ. Surfactant replacement therapy for meconium aspiration syndrome: Pediatrics 1996;97:48-52.
Lotze A, Mitchell BR, Bulas DI, Zola EM, Shalwitz RA, Gunkel JH, and the Survanta In Term Infants Study Group: Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. J Pediatr 1998;132:40-7.
Willson DF, Zaritsky A, Bauman LA, Dockery K, James RL, Conrad D, Craft H, Novotny WE, Egan EA, Dalton H: Instillation of calf lung surfactant extract (calfactant) is beneficial in pediatric acute hypoxemic respiratory failure. Crit Care Med 1999;27:188-95.
Wiswell TE, Knight GR, Finer NN, Donn SM, Desai H, Walsh WF, Sekar KC, Bernstein G, Keszler M, Visser VE, Merritt TA, Mannino FL, Mastrioianni L, Marcy B, Revak SD, Tsai H, Cochrane CG: A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome. Pediatrics. 2002;109:1081-7.
Surfactant therapy was found to improve respiratory function in some parenchymal lung diseases other than RDS. In addition, early intervention as well as a multi-dose regimen appeared to impact efficacy |
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The groundwork for surfactant replacement
for meconium aspiration syndrome is founded in in vitro and
in animal experiments in which meconium inhibited/inactivated surfactant
function; this inhibition was reversed in a dose-dependent manner with
exogenous surfactant. Findlay and colleagues randomized 40 term infants
with (MAS) who required ventilatory support to a course of Survanta
(up to four doses at 6 hour intervals) or air placebo. Infants had moderate
respiratory dysfunction with mean OIs in the low 20s. Survanta-treated
infants demonstrated a mild improvement after the initial dose, but
exhibited a dramatic decrease in OI following second and third doses.
Only one of the 20 Survanta-treated infants vs. 6 of 20 control infants
required ECMO support. The durations of mechanical ventilation, oxygen
therapy, and hospitalization were significantly lower in the Survanta
treated group.
A larger study (n=328) by Lotze et al expanded the use of Survanta to
the treatment of infants with sepsis/pneumonia and PPHN in addition
to meconium aspiration syndrome. Infants were randomized by disease
and by OI strata to treatment with surfactant or air-placebo. The need
for ECMO was designated as the primary outcome variable. Survanta treatment
did not change mortality but was associated with a 27% reduction (from
40.4% to 29.7%) in the need for ECMO. This treatment effect was greatest
(40%) in infants with sepsis, intermediate (27%) in infants with meconium
aspiration syndrome (MAS), and not significant (7%) in infants with
PPHN. Also of note was the observation that a significant improvement
in the primary outcome was seen only among infants who at the time of
study entry had the least severe disease (OIs 15-22). Contrary to the
Findlay study, no differences in durations of ventilation or hospitalization
were noted.
Our critical care colleagues, headed by Willson, have reported one small (n=42) randomized unmasked trial of Infasurf for the treatment of children with acute hypoxemic respiratory failure characterized by need for ventilatory support, an OI > 7, and radiographic findings of diffuse bilateral pulmonary infiltrates. Children treated with Infasurf demonstrated more rapid improvement in respiratory function and were extubated 4 days sooner and hospitalized 5 days less compared to control patients. (See also Moller JC, et al in SOURCES FOR ADDITIONAL INFORMATION)
More recently, Wiswell et al reported a unique randomized trial in term and near-term infants with MAS treated with Surfaxin, a synthetic surfactant composed of phospholipids and a synthetic peptide designed as an analog surfactant protein B. The treatment intervention consisted of three serial bronchoalveolar lung lavages, each employing 8 mL/kg of dilute Surfaxin. Surfaxin lavage reduced OI for 96 hours after treatment and resulted in a non-significant reduction in duration of ventilation. No side effects of treatment were noted in this initial study.
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Findlay RD, Taeusch HW, Walther FJ. Surfactant replacement therapy for meconium aspiration syndrome: Pediatrics 1996;97:48-52.
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Lotze A, Mitchell BR, Bulas DI, Zola EM, Shalwitz RA, Gunkel JH, and the Survanta In Term Infants Study Group: Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. J Pediatr 1998;132:40-7.
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Willson DF, Zaritsky A, Bauman LA, Dockery K, James RL, Conrad D, Craft H, Novotny WE, Egan EA, Dalton H: Instillation of calf lung surfactant extract (calfactant) is beneficial in pediatric acute hypoxemic respiratory failure. Crit Care Med 1999;27:188-95.
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(For non-journal subscribers, an additional fee may apply for full text article)
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view journal abstract |
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Wiswell TE, Knight GR, Finer NN, Donn SM, Desai H, Walsh WF, Sekar KC, Bernstein G, Keszler M, Visser VE, Merritt TA, Mannino FL, Mastrioianni L, Marcy B, Revak SD, Tsai H, Cochrane CG: A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome. Pediatrics. 2002;109:1081-7
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(For non-journal subscribers, an additional fee may apply for full text article)
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Clinical Expression of Defects in Surfactant Proteins B and C
Nogee LM, deMello DE, Dehner LP, Colten HR: Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 1993;328:406-410.
Nogee LM, Dunbar AE, III, Wert SE, Askin F, Hamvas A, Whitsett JA: A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med 2001;344:573-579.
Tredano M, Griese M, de Blic J, et al. Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: relationship to SFTPB Am J Med Genet 2003; 119A:324-39.
Thomas AQ, Lane K, Phillips J, et al. Heterozygosity for a Surfactant Protein C Gene Mutation Associated with Usual Interstitial Pneumonitis or Cellular Nonspecific Interstitial Pneumonitis in One Kindred. Am J Respir Crit Care Med 2002; 165:1322-1328.
Animal derived exogenous surfactant preparations contain the hydrophobic surfactant proteins SP-B and SP-C. Surfactant replacement experiments in animal models and evidence from genetically engineered mice models have demonstrated the importance of these proteins in surfactant function. Different mutations of the SP-B and SP-C genes are now recognized to cause a varied phenotype of respiratory disease ranging from lethality in the neonatal period to chronic disease in adults. |
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The first inborn error of surfactant metabolism was identified in 1993 in an infant with fatal, autosomal recessive lung disease associated with SP-B deficiency due to a frameshift mutation in the SP-B gene. More than 25 mutations of the SP-B gene have since been identified, including mutations that allow for synthesis of reduced amounts of SP-B and milder lung disease. Reduced amounts of SP-C due to an impairment of its processing from its precursor protein may also contribute to the lung disease.
The typical clinical scenario for SP-B deficiency involves a full-term neonate who presents immediately with, or who insidiously develops, severe respiratory distress with bilateral diffuse alveolar and interstitial infiltrates on chest radiograph. Surfactant therapy, especially with a preparation that contains SP-B, may result in transient improvement early in the course. Lung disease is progressive and fatal without lung transplantation. Definitive diagnosis requires finding mutations on both alleles of the SP-B gene. Infants who appear to be SP-B deficient but who do not have an abnormality in the SP-B gene have been identified. These infants may have defects in other genes, such as enzymes or other proteins important in the processing of SP-B, resulting in the same phenotype.
In a 2001 report, Nogee and co-workers described an infant who presented at six weeks of age with tachypnea and cyanosis, chest radiographic findings of increased interstitial markings, and a family history of interstitial lung disease inherited in an autosomal dominant fashion. SP-C was undetectable in the child's lung tissue. A mutation on one allele of the SP-C gene that led to production of an abnormal SP-C precursor protein was identified. It was suggested that respiratory disease occurred due to a dominant negative influence of the abnormal protein on SP-C metabolism or function. Thomas et al. reported a very large family within which autosomal dominant pulmonary fibrosis was associated with a mutation in the SP-C gene, with considerable variability in the age of onset of lung disease and lung pathology.
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Nogee LM, deMello DE, Dehner LP, Colten HR: Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 1993;328:406-410.
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Nogee LM, Dunbar AE, III, Wert SE, Askin F, Hamvas A, Whitsett JA: A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med 2001;344:573-579.
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Tredano M, Griese M, de Blic J, et al. Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: relationship to SFTPB Am J Med Genet 2003; 119A:324-39.
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Thomas AQ, Lane K, Phillips J, et al. Heterozygosity for a Surfactant Protein C Gene Mutation Associated with Usual Interstitial Pneumonitis or Cellular Nonspecific Interstitial Pneumonitis in One Kindred. Am J Respir Crit Care Med 2002; 165:1322-1328.
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| Accreditation back to top |
| Physicians |
The Johns Hopkins University School of Medicine is accredited
by the Accreditation Council for Continuing Medical Education to provide
continuing medical education for physicians.
|
| Nurses |
The
Institute for Johns Hopkins Nursing is accredited as a provider of
continuing education in nursing by the American Nurses Credentialing
Center's Commission on Accreditation.
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| Credit Designations back to top |
| Physicians |
The
Johns Hopkins University School of Medicine designates this educational
activity for a maximum of 0.5 category 1 credits toward the AMA
Physician's Recognition Award. Each physician should claim only those
credits that he/she actually spent in the activity.
|
| Nurses |
The Institute for Johns Hopkins Nursing designates this activity for a maximum of 0.5 contact hours for this eNewsletter.
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| Respiratory Therapists |
Contact
your state licensing board to confirm that AMA PRA category 1 credits
are accepted toward fulfillment of RT requirements.
|
| Target Audience back to top |
This
activity has been developed for Neonatologists, NICU Nurses and
Respiratory Therapists working with Neonatal patients. There are no
fees or prerequisites for this activity.
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| Learning Objectives back to top |
The
Johns Hopkins University School of Medicine and The Institute for Johns
Hopkins Nursing take responsibility for the content, quality, and
scientific integrity of this CE activity. At the conclusion of this
activity, participants should be able to:
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• |
Evaluate the research presented to develop a more complete understanding of the use of surfactant preparations.
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• |
Demonstrate a more complete understanding of the advantages/disadvantages of surfactant therapy for both RDS and non-RDS diseases.
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• |
Use the information presented herein as a basis for decision making in determining prophylaxis vs rescue use of surfactants in your clinical practice.
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| Full Disclosure Policy Affecting CME Activities back
to top |
As providers accredited by the Accreditation Council for
Continuing Medical Education and American Nursing Credentialing Center,
it is the policy of The Johns Hopkins University School of Medicine
and The Institute of Johns Hopkins Nursing to require the disclosure
of the existence of any significant financial interest or any other
relationship a faculty member or a provider has with the manufacturer(s)
of any commercial product(s) discussed in an education presentation.
The presenting faculty reported the following:
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• |
Dr.
Nogee has indicated a financial relationship of grant/research support
with Forest Laboratories and has received an honorarium from Forest
Laboratories.
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|
• |
Dr.
Lawson has indicated a financial relationship of grant/research support
from the NIH. He also receives financial/material support from Nature
Publishing Group as the Editor of the Journal of Perinatology.
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All other faculty have indicated that they have not received financial
support for consultation, research, or evaluation, nor have financial
interests relevant to this e-Newsletter.
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| Unlabelled/Unapproved Uses back to top |
In
accordance with the ACCME and ANCC Standards for Commercial Support,
the audience is advised that one or more presentations in this
continuing education activity may contain reference(s) to unlabeled or
unapproved uses of drugs or devices.
No faculty member has indicated that their presentation will include information on off label products.
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| Disclaimers back to top |
The
opinions and recommendations expressed by faculty and other experts
whose input is included in this program are their own. This enduring
material is produced for educational purposes only. Use of The Johns
Hopkins University name implies review of education format design and
approach. Please review the complete prescribing information of
specific drugs or combination of drugs, including indications,
contraindications, warnings, and adverse effects before administering
pharmacologic therapy to patients.
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| Internet CE Policy back to top |
The
Offices of Continuing Education (CE) at The Johns Hopkins University
School of Medicine and The Institute for Johns Hopkins Nursing are
committed to protect the privacy of its members and customers. The
Johns Hopkins University maintains its Internet site as an information
resource and service for physicians, other health professionals and the
public.
The Johns Hopkins University School of Medicine and The
Institute For Johns Hopkins Nursing will keep your personal and credit
information confidential when you participate in a CE Internet based
program. Your information will never be given to anyone outside The
Johns Hopkins University program. CE collects only the information
necessary to provide you with the service you request.
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| Copyright |
© JHUSOM, IJHN, and eNeonatal Review
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