PurposeAirway stents (AS) are a last-resort treatment for central airway obstructions when airway patency cannot be maintained above 50%, in patients unsuitable for surgery, or with recurrence after surgery. However, AS placement can cause complications, including life-threatening mucostasis, which is challenging to manage. Standard methods to prevent mucus retention often have limited efficacy. Dornase alfa, a mucolytic agent widely used in cystic fibrosis (CF) patients, has shown efficacy in secretion control in mechanically ventilated pediatric non-CF patients. This study evaluates the efficacy and safety of nebulized dornase alfa in managing AS-related life-threatening mucostasis.ResultsFourteen patients (mean age 56.3 ± 15.6 years) with life-threatening mucostasis were identified among 255 stented patients (2017–2019). Eight had Y-shaped stents, and 6 had non-Y-shaped stents (5 hourglass and 1 OKI); 13 stents were placed for benign conditions and 1 for malignancy. Mucus grades (defined by Marchese et al.) and the number of bronchoscopies needed 6 months before and after dornase alfa were evaluated. Statistically significant decreases were observed in both mucus grades (2.36 ± 0.49 to 0.79 ± 0.59, p < 0.001) and the number of bronchoscopies per patient (3.21 ± 0.89 to 2.00 ± 1.04, p = 0.002). The shape of AS and the presence of bronchiectasis on thoracic computed tomography scans had no significant impact on mucostasis development. No side effects related to dornase alfa were observed.ConclusionDornase alfa significantly reduced mucus burden and bronchoscopic interventions in AS-related life-threatening mucostasis, demonstrating its safety and efficacy for managing this complication.

Prinflammatory extracellular chromatin from neutrophil extracellular traps (NETs) and other cellular sources is found in COVID-19 patients and may promote pathology. We determined whether pulmonary administration of the endonuclease dornase alfa reduced systemic inflammation by clearing extracellular chromatin. Eligible patients were randomized (3:1) to the best available care including dexamethasone (R-BAC) or to BAC with twice-daily nebulized dornase alfa (R-BAC + DA) for seven days or until discharge. A 2:1 ratio of matched contemporary controls (CC-BAC) provided additional comparators. The primary endpoint was the improvement in C-reactive protein (CRP) over time, analyzed using a repeated-measures mixed model, adjusted for baseline factors. We recruited 39 evaluable participants: 30 randomized to dornase alfa (R-BAC +DA), 9 randomized to BAC (R-BAC), and included 60 CC-BAC participants. Dornase alfa was well tolerated and reduced CRP by 33% compared to the combined BAC groups (T-BAC). Least squares (LS) mean post-dexamethasone CRP fell from 101.9 mg/L to 23.23 mg/L in R-BAC +DA participants versus a 99.5 mg/L to 34.82 mg/L reduction in the T-BAC group at 7 days; p=0.01. The anti-inflammatory effect of dornase alfa was further confirmed with subgroup and sensitivity analyses on randomised participants only, mitigating potential biases associated with the use of CC-BAC participants. Dornase alfa increased live discharge rates by 63% (HR 1.63, 95% CI 1.01-2.61, p=0.03), increased lymphocyte counts (LS mean: 1.08 vs 0.87, p=0.02) and reduced circulating cf-DNA and the coagulopathy marker D-dimer (LS mean: 570.78 vs 1656.96 μg/mL, p=0.004). Dornase alfa reduces pathogenic inflammation in COVID-19 pneumonia, demonstrating the benefit of cost-effective therapies that target extracellular chromatin. LifeArc, Breathing Matters, The Francis Crick Institute (CRUK, Medical Research Council, Wellcome Trust). NCT04359654.

Background: Prinflammatory extracellular chromatin from neutrophil extracellular traps (NETs) and other cellular sources is found in COVID-19 patients and may promote pathology. We determined whether pulmonary administration of the endonuclease dornase alfa reduced systemic inflammation by clearing extracellular chromatin. Methods: Eligible patients were randomized (3:1) to the best available care including dexamethasone (R-BAC) or to BAC with twice-daily nebulized dornase alfa (R-BAC + DA) for seven days or until discharge. A 2:1 ratio of matched contemporary controls (CC-BAC) provided additional comparators. The primary endpoint was the improvement in C-reactive protein (CRP) over time, analyzed using a repeated-measures mixed model, adjusted for baseline factors. Results: We recruited 39 evaluable participants: 30 randomized to dornase alfa (R-BAC +DA), 9 randomized to BAC (R-BAC), and included 60 CC-BAC participants. Dornase alfa was well tolerated and reduced CRP by 33% compared to the combined BAC groups (T-BAC). Least squares (LS) mean post-dexamethasone CRP fell from 101.9 mg/L to 23.23 mg/L in R-BAC +DA participants versus a 99.5 mg/L to 34.82 mg/L reduction in the T-BAC group at 7 days; p=0.01. The anti-inflammatory effect of dornase alfa was further confirmed with subgroup and sensitivity analyses on randomised participants only, mitigating potential biases associated with the use of CC-BAC participants. Dornase alfa increased live discharge rates by 63% (HR 1.63, 95% CI 1.01–2.61, p=0.03), increased lymphocyte counts (LS mean: 1.08 vs 0.87, p=0.02) and reduced circulating cf-DNA and the coagulopathy marker D-dimer (LS mean: 570.78 vs 1656.96 μg/mL, p=0.004). Conclusions: Dornase alfa reduces pathogenic inflammation in COVID-19 pneumonia, demonstrating the benefit of cost-effective therapies that target extracellular chromatin. Funding: LifeArc, Breathing Matters, The Francis Crick Institute (CRUK, Medical Research Council, Wellcome Trust). Clinical trial number: NCT04359654 .

Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review. To determine whether the timing of dornase alfa inhalation (in relation to airway clearance techniques or morning versus evening inhalation) has an impact on objective and subjective measures of clinical efficacy in people with cystic fibrosis. Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, thePhysiotherapy Evidence Database (PEDro), clinical trial registries and international cystic fibrosis conference proceedings. Date of the most recent search: 12 October 2020. Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the trial with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We assessed the quality of the evidence using GRADE. We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant. In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence). The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day.Further research is warranted.

Withdrawal of dornase alfa increases ventilation inhomogeneity in children with cystic fibrosis

BackgroundMechanically ventilated patients with coronavirus disease 2019 (COVID-19) have a mortality of 24–53%, in part due to distal mucopurulent secretions interfering with ventilation. Dornase alfa is recombinant human DNase 1 and digests DNA in mucoid sputum. Nebulized dornase alfa is FDA-approved for cystic fibrosis treatment. DNA from neutrophil extracellular traps (NETs) contributes to the viscosity of mucopurulent secretions. NETs are found in the serum of patients with severe COVID-19, and targeting NETs reduces mortality in animal models of acute respiratory distress syndrome (ARDS). Thus, dornase alfa may be beneficial to patients with severe COVID-19—acting as a mucolytic and targeting NETs. However, delivery of nebulized drugs can aerosolize SARS-CoV-2, which causes COVID-19, increasing the infection risk for staff. Here, we report a single center case series where dornase alfa was administered through an in-line nebulizer system to minimize risk of virus aerosolization.MethodsDemographic, clinical data, and outcomes were collected from the electronic medical records of five mechanically ventilated patients with COVID-19—including three requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO)—treated with nebulized in-line endotracheal dornase alfa co-administered with albuterol (used to increase delivery to the alveoli), between March 31 and April 24, 2020. Data on tolerability and responses, including longitudinal values capturing respiratory function and inflammatory status, were analyzed.ResultsFollowing nebulized in-line administration of dornase alfa with albuterol, the fraction of inspired oxygen requirements was reduced for all five patients. All patients remain alive and two patients have been discharged from the intensive care unit. No drug associated toxicities were identified.ConclusionsThe results presented in this case series suggest that dornase alfa will be well-tolerated by critically ill patients with COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and two have recently been registered (NCT04359654 and NCT04355364). With this case series, we hope to contribute to the development of management approaches for critically ill patients with COVID-19.

Lung transplant (LTx) recipients are at risk of lower respiratory tract infection (LRTI), while altered physiology may lead to difficulty clearing sputum. Mucoactive agents alter sputum properties and facilitate mucociliary clearance; however, there are no randomized controlled trials (RCTs) studying this post-LTx. This RCT evaluated the safety and efficacy of nebulized dornase alfa during LRTI post-LTx. Inpatient adults with LRTI and abnormal sputum following bilateral sequential LTx were eligible. Participants received 5ml of isotonic saline, or 2.5ml of dornase alfa, nebulized once daily for 1month followed by 2months symptom diary. Primary outcome was lung clearance index (LCI2%). Secondary outcomes included spirometry, quality of life, readmission, length of stay, self-reported exacerbations, and adverse events at baseline, 1 and 3months. Thirty-two participated, 16 in each group, baseline mean (SD) FEV1 % 58 (22), median (IQR) length of stay 7 (5) days, time since LTx 3.49 (6.80) years. There were no significant between-group differences in LCI2% at any point (1month mean difference -0.34, 95% confidence interval (CI) -1.57 to 0.89; 3months -0.76, 95% CI -2.29 to 0.78, favoring dornase alfa). Secondary outcomes were not different between groups. These results do not support the routine use of dornase alfa during LRTI in LTx recipients.

Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review. To determine whether the timing of dornase alfa inhalation (in relation to airway clearance techniques or morning versus evening inhalation) has an impact on objective and subjective measures of clinical efficacy in people with cystic fibrosis. Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), clinical trial registries and international cystic fibrosis conference proceedings.Date of the most recent search: 06 June 2018. Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the trial with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence). The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day.Further research is warranted.

Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane review. To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day). Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the most recent search: 25 April 2016. Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We identified 115 trial reports representing 55 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second. Similarly, forced vital capacity and quality of life were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small studies in children (seven to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms. The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alpha inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day.Further research is warranted.

Chronic Rhinosinusitis in Patients with Cystic Fibrosis

BackgroundNebulised dornase alfa is used off-label in critically ill patients. We aimed to assess the benefits and harms of nebulised dornase alfa versus placebo, no prophylaxis, or hypertonic saline on patient-important outcome measures in adult critically ill patients.MethodsWe performed a systematic review with meta-analysis and trial sequential analysis (TSA) using the Cochrane Collaboration methodology. Eligible trials were randomised clinical trials comparing nebulised dornase alfa with placebo, no prophylaxis, or hypertonic saline. The predefined outcome measures were all-cause mortality, duration of mechanical ventilation, length of stay, and adverse events. Two reviewers independently assessed trials for inclusion, data extraction, and risk of bias. Risk ratios (RRs) with 95 % confidence intervals (CIs) were estimated by conventional cumulative meta-analysis, and the robustness of the primary estimate was assessed by TSA.ResultsTwo trials (n = 63) were included; both were judged to have high risk of bias. There was no statistically significant difference in mortality (random effects model RR (95 % CI) 0.73 (0.09–5.77); P = 0.24; I2 = 30 %). TSA could not be conducted because less than 1 % of the required information size had been accrued. None of the two trials reported adequate and detailed data on any of the secondary outcome measures.ConclusionsWe found very low quantity and quality of evidence for use of nebulised dornase alfa in adult critically ill patients in this systematic review with meta-analysis.Systematic review registrationThe International Prospective Register of Systematic Reviews (PROSPERO), no. CRD442015016047.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-015-0142-z) contains supplementary material, which is available to authorized users.

Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day). Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international CF conference proceedings.Date of the most recent search: 22 February 2013. Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We identified 99 trial reports representing 48 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change FEV1. Similarly, FVC and quality of life were not significantly affected; FEF25 was significantly worse with dornase alfa inhalation after airway clearance, MD -0.17 litres (95% CI -0.28 to -0.05), based on the pooled data from two small studies in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms. The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alpha inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day.Further research is warranted.

Small-airways deposition of dornase alfa in children with asthma and persistent airway obstruction

Inhaled Dornase alfa (Pulmozyme) as a noninvasive treatment of atelectasis in mechanically ventilated patients

Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day). Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international CF conference proceedings.Search date: 6 October 2010. Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We identified 92 trial reports representing 47 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change FEV(1). Similarly, FVC and quality of life were not significantly affected; FEF(25) was significantly worse with dornase alfa inhalation after airway clearance, MD -0.17 litres (95% CI -0.28 to -0.05), based on the pooled data from two small studies in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms. The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow-up. Apart from this, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day.Further research is warranted.

To increase clinician adherence to prescribing guidelines for pulmonary medications in children with cystic fibrosis (CF). Quality improvement project with multiple time series design. The CF center at a tertiary care pediatric hospital in the United States. Children with CF who were eligible to receive oral azithromycin, nebulized dornase alfa, or inhaled tobramycin sulfate based on prescribing guidelines for CF lung disease. Evidence-based prescribing guidelines were designed by a local committee to reflect consensus recommendations from the CF Foundation. Clinicians and families were educated about guidelines. Adherence to prescribing guidelines was tracked using a local CF database and record reviews. Weekly meetings were used to highlight adherence failures and promote clinician accountability. The rate of clinician adherence to prescribing guidelines. One hundred seventy patients with CF were included. At the start of the project, the rate of clinician adherence to prescribing guidelines was 62%. After 3 months of the project, the rate of clinician adherence to prescribing guidelines was 87% (odds ratio = 4.6; 95% confidence interval, 3.0-7.0). The improvements in adherence to prescribing guidelines were sustained for 21 months of follow-up. Educating clinicians about prescribing guidelines, sharing guidelines with families, and monitoring clinician adherence improve prescribing adherence to evidence-based recommendations.

Effect Of Nebulized Dornase Alfa On Pulmonary Gas Exchange In Critically Ill Stem Cell Transplant Recipients

Long-term use of nebulized human recombinant DNase1 in two siblings with primary ciliary dyskinesia

Source: Wang SS, O’Leary LA, FitzSimmons SC, et al. The impact of early cystic fibrosis diagnosis on pulmonary function in children. J Pediatr. 2002;141:804–810.To determine whether early diagnosis of cystic fibrosis (CF) had an impact on the severity of lung damage at ages 6 to 10 years, investigators from the Centers for Disease Control and the Cystic Fibrosis Foundation retrospectively reviewed patient data gathered by the Cystic Fibrosis Foundation National Patient Registry on 3,625 children whose CF diagnosis was established by 36 months of age between 1982 and 1990 and who were followed regularly through childhood. Patients were categorized into 4 groups according to whether they were diagnosed before or after age 6 weeks and whether they were asymptomatic versus symptomatic at diagnosis. Asymptomatic diagnosis was defined as diagnosis by family history, genotype, prenatal diagnosis, or neonatal screening. Babies diagnosed because of meconium ileus were excluded. The forced expiratory volume in 1 second (FEV1) was used as the primary measurement of lung damage. The registry’s database includes the FEV1 recorded at each patient’s annual visit. Values for FEV1 less than 40% predicted were considered severe, less than 70% were considered moderate, and less than 90% were considered impaired. Factors considered in the analysis included gender, birth year, pancreatic status, geographic location, genotype, and weight and height percentiles. Race, geography, and pancreatic status were included in the final regression analysis.There were 157 children in the early asymptomatic diagnosis (EAD) group, 227 in the early symptomatic diagnosis (ESD) group, 161 in the late asymptomatic diagnosis (LAD) group, and 3,080 in the late symptomatic diagnosis (LSD) group. The median age of diagnosis was 3.6 weeks for the EAD group, 4.2 weeks for the ESD group, 11.4 weeks for the LAD group, and 25 weeks for the LSD group. There were significant differences between the groups for race, year of birth, geography, and growth parameters but no differences for gender, ethnicity, or delta F508 mutations. There was no difference in group mean FEV1 when analyzed for all patients. However, when stratified by birth age (before 1987 and after 1987) the EAD group born after 1987 had higher mean FEV1 values at 6 and 8 years of age (P< 05) than those 05) than those in other groups. A lower percentage of children in the EAD group born after 1987 had moderate to severe lung disease than children in other diagnostic groups (P< 05). Adjusting 05). Adjusting for race, gender, pancreatic status, and place of birth, CF patients 6–10 years of age born after 1987 had a greater likelihood of moderate-to-severe pulmonary disease in the ESD group (Odds Ratio 2.17; 95% CI, 0.91–5.21), the LAD group (OR 2.18; 95% CI, 0.88–5.35), and the LSD group (OR=2.12; 95% CI, 0.97–4.64) compared to the EAD group, all differences that did not achieve statistical significance. The slope of the decline in FEV1 between ages 6 and 10 years appeared parallel in all 4 groups. As expected the EAD group had fewer children with poor growth parameters than the other groups. The authors conclude that early diagnosis of CF is likely to improve pulmonary function later in childhood, a possible outcome of early and aggressive therapy.Pulmonary dysfunction is responsible for the majority of morbidity and mortality in CF, so the suggestion that pulmonary status may be favorably influenced by early diagnosis is encouraging. Although only Wisconsin, Colorado, and Wyoming are currently routinely screening newborns for CF, many other states are considering implementation of screening. One of the barriers to adopting screening for CF has been uncertainty about whether early diagnosis affects outcome. Nutritional benefits of early diagnosis have been documented,1 and this study adds important information suggesting that pulmonary function may also benefit from early diagnosis. The benefits in improved FEV1 were seen only in the children born after 1987, a cut-off year the authors chose only because there appeared to be a natural break around this year. This could be related to important advances in our understanding of the pulmonary patho physiology of CF, more aggressive management of infection, and newer therapeutic options such as nebulized dornase alfa (DNase) and nebulized TOBI.Primary care physicians working in states without newborn CF screening should be alert to a family history suggestive of CF to facilitate prenatal diagnosis and early intervention.

Nebulised dornase alfa an option in young children with CF?