Adapting the cystic fibrosis care model: Perspectives from people with CF, caregivers, and members of CF care teams.

BACKGROUND: Rapidly emerging clinical trends offer the opportunity to amend guidance on issues pertaining to CF care delivery. A national survey was conducted to gather perspectives on CF care including potential adaptations to the care model to best meet the needs of this population. METHODS: A survey instrument was developed to capture perspectives on CF care. People with CF (pwCF), including those post lung transplant, caregivers and care teams were surveyed. Descriptive statistics were calculated to characterize respondents and responses. RESULTS: In-person, routine visits with the CF care teams were valued by survey respondents. However, reduced in-person visit frequency from the standard three-month interval was supported for individuals in a stable state of health. This was particularly true for pwCF ages two or older and on a modulator. Lung function, pulmonary exacerbation frequency, and transition periods were noted to influence preference for visit frequency. Integrating telehealth with remote monitoring in between visits was broadly supported. For shared care between CF teams and other medical providers (transplant teams and primary care providers (PCP)), good communication, easily accessible health records, and convenient locations were important. CONCLUSIONS: Survey findings support adapting CF care based on individual needs and life transitions. Themes identified can inform future areas of study and resource development to support successful modification of the CF care model and shared decision-making between patients and their care providers.

Cystic fibrosis foundation position paper: Redefining the cystic fibrosis care team.

Interdisciplinary teams care for people with cystic fibrosis (pwCF) at specialized treatment centers. These teams have laid the foundation for the cystic fibrosis (CF) care model responsible for gains in health outcomes and quality of life within the CF community. However, the landscape of CF care is transforming, invigorated by new technologies, accessibility of cystic fibrosis transmembrane conductance regulator (CFTR) therapies, and increased utilization of telemedicine. In light of these advances, it is appropriate to re-evaluate the CF care team structure. This position paper offers guidance for the structure of a CF care center designed to meet the evolving needs of the CF community. Fundamental to the proposed center structure is recognition of pwCF and their families as integral members of their care teams, underpinning the necessity for shared decision making, awareness of social determinants of health, and active partnership between all healthcare professionals involved in the care of pwCF.

Practical Guidance for Clinical Microbiology Laboratories: Updated guidance for processing respiratory tract samples from people with cystic fibrosis.

SUMMARYThis guidance presents recommendations for clinical microbiology laboratories for processing respiratory samples from people with cystic fibrosis (pwCF). Appropriate processing of respiratory samples is crucial to detect bacterial and fungal pathogens, guide treatment, monitor the epidemiology of cystic fibrosis (CF) pathogens, and assess therapeutic interventions. Thanks to CF transmembrane conductance regulator modulator therapy, the health of pwCF has improved, but as a result, fewer pwCF spontaneously expectorate sputum. Thus, the collection of sputum samples has decreased, while the collection of other types of respiratory samples such as oropharyngeal and bronchoalveolar lavage samples has increased. To optimize the detection of microorganisms, including Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Burkholderia cepacia complex; other less common non-lactose fermenting Gram-negative bacilli, e.g., Stenotrophomonas maltophilia, Inquilinus, Achromobacter, Ralstonia, and Pandoraea species; and yeasts and filamentous fungi, non-selective and selective culture media are recommended for all types of respiratory samples, including samples obtained from pwCF after lung transplantation. There are no consensus recommendations for laboratory practices to detect, characterize, and report small colony variants (SCVs) of S. aureus, although studies are ongoing to address the potential clinical impact of SCVs. Accurate identification of less common Gram-negative bacilli, e.g., S. maltophilia, Inquilinus, Achromobacter, Ralstonia, and Pandoraea species, as well as yeasts and filamentous fungi, is recommended to understand their epidemiology and clinical importance in pwCF. However, conventional biochemical tests and automated platforms may not accurately identify CF pathogens. MALDI-TOF MS provides excellent genus-level identification, but databases may lack representation of CF pathogens to the species-level. Thus, DNA sequence analysis should be routinely available to laboratories for selected clinical circumstances. Antimicrobial susceptibility testing (AST) is not recommended for every routine surveillance culture obtained from pwCF, although selective AST may be helpful, e.g., for unusual pathogens or exacerbations unresponsive to initial therapy. While this guidance reflects current care paradigms for pwCF, recommendations will continue to evolve as CF research expands the evidence base for laboratory practices.

Factors associated with listing for lung transplantation in IPF patients: An analysis of the pulmonary fibrosis foundation registry.

Rationale and objectives: Lung transplantation is a potentially life-saving treatment option for patients with idiopathic pulmonary fibrosis (IPF); however, not all eligible candidates get referred and listed for transplantation. Amongst IPF patients within the Pulmonary Fibrosis Foundation Patient Registry (PFF-R), we sought to determine the proportion of patients who undergo lung transplant listing and the characteristics associated with transplant listing. Methods: An analysis of IPF patients with at least six months of follow-up data was performed. Patients with well-established contraindications to lung transplantation were excluded. Two complementary analyses were performed. The "prevalent" population included all patients with IPF at time of enrollment into the registry. The "incident severe" population included all patients with IPF who progressed to GAP Stage 3. Results: Of the 2003 patients in the PFF-R, 475 patients were included in the "prevalent" population. Of this group, only 42 (8.8%) were either listed for or underwent lung transplant. Univariable analysis of the "prevalent" population found age (per 10 year increase, OR 0.531, p = 0.0025), percent predicted FVC (OR 0.572, p=<0.0001), percent predicted DLCO (OR 0.606, p < 0.0001), 6-min walk distance (per 50 m, OR 0.831, p = 0.019), and oxygen use at rest (OR 5.157, p < 0.0001) were predictive of listing. On multivariable analysis, age (per 10 year increase, OR 0.558, p = 0.0088), percent predicted FVC (OR 0.728, p = 0.0161), and oxygen use at rest (OR 3.264, p = 0.0029) remained significant predictors for lung transplant listing. The "incident severe" group consisted of 176 patients (8.8%). 24 patients (13.6%) from this cohort were either listed for or received a transplant. Only age (per 10 year increase, OR 0.0286, p = 0.0465) was associated with transplant listing on univariable analysis in the Incident severe population. Conclusion: Only a small proportion of potentially eligible patients with IPF are listed for lung transplantation, even when seen at pulmonary fibrosis centers of excellence. Advanced age appears to be the primary factor associated with failure to be listed. Further refinement of future registry data is required to more clearly delineate exact reasons for low rates of listing.

Prevalence of pulmonary hypertension in patients with COVID-19 related lung disease listed for lung transplantation: A UNOS registry analysis.

COVID-19 related lung disease (CRLD) has emerged as an indication for lung transplantation (LT) in highly select patients. The prevalence and prognostic implication of coexisting pulmonary hypertension (PH) in patients with CRLD listed for LT is not known. Adult patients in the United Network for Organ Sharing database listed for LT for COVID-19 related acute respiratory distress syndrome or fibrosis through March 2022 were identified. The prevalence and impact of precapillary PH on pre- and posttransplantation survival was determined. Time-to-event analysis was used to compare outcomes between those with and without precapillary PH. We identified 245 patients listed for LT for CRLD who had right heart catheterization data available at the time of registry listing. Median age of the cohort was 54 years (interquartile range [IQR]: 46, 60), 56 (22.9%) were female, and the median lung allocation score was 81.3 (IQR: 53.3, 89.4). The prevalence of precapillary PH at the time of transplant listing was 27.9%. There was no significant difference in pretransplant mortality in patients with and without precapillary PH (sHR: 0.5; 95% confidence interval [CI]: 0.1-1.7, p = 0.261). A total of 187 patients ultimately underwent LT; of those, 60 (31.0%) were identified as having precapillary PH during the waitlist period. Posttransplantation survival was similar between patients with and without pretransplant precapillary PH (hazard ratio: 0.96; 95% CI: 0.2-3.7, p = 0.953). We observed a high rate of concomitant precapillary PH in patients listed for LT for CRLD. Though common, coexisting precapillary PH was not associated with a significant difference in either pre- or post-transplantation outcomes.

Cystic fibrosis prevalence in the United States and participation in the Cystic Fibrosis Foundation Patient Registry in 2020.

BACKGROUND: The Cystic Fibrosis Foundation Patient Registry (CFFPR) collects data on individuals with cystic fibrosis (CF) in the United States (US). In 2012, the US CF population was estimated at 33,292 to 34,327 individuals, with 81-84% CFFPR participation. METHODS: In this study, we update these estimates via simulation to account for uncertainty in CF incidence by race or Hispanic ethnicity, initiation of CF newborn screening (NBS) programs by state, and updated cumulative survival for CF births 1968-2020. We defined registry participation as the proportion of individuals alive as of 2020 with any prior CFFPR participation as well as the proportion with contributing data in 2019 or 2020; we summarize CFFPR participation for those born prior to 1968. RESULTS: We estimated the 2020 prevalent CF population between 1968-2020 to be 38,804 (95% Uncertainty Interval (UI): 38,532 to 39,065) individuals, with 77% of the prevalent CF population contributing recent data. CFFPR participation differs by age (54% of those born in 1968) and exceeds >90% of the population born in 2009 or later. CONCLUSIONS: We demonstrate that the CFFPR remains a valid data source generalizable to the CF population. High participation among younger individuals may reflect the success of newborn screening programs and early referral to CF care. If engagement can be sustained, the percentage of individuals participating in the CFFPR will grow over time and there is an opportunity to identify factors associated with loss to follow up among older individuals to optimize the quality of the CFFPR data.

Remote ex vivo lung perfusion at a centralized evaluation facility.

BACKGROUND: In the US, only 23% of lungs offered for transplantation are transplanted. Ex vivo lung perfusion (EVLP) allows for evaluation of additional donor lungs; its adoption has been limited by resources and expertise. Dedicated facilities with a centralized lung evaluation system (CLES) could expand access to EVLP. METHODS: In this unblinded, nonrandomized, traditional feasibility study, 7 US transplant centers referred lungs declined for standard transplantation to a dedicated EVLP facility, which utilized a CLES. EVLP was remotely monitored by the transplant teams. CLES lungs were matched with contemporaneous conventional static cold-preserved controls at each center. RESULTS: A total of 115 recipients were enrolled, and 66 received allografts from 63 donors after EVLP at the dedicated CLES facility. Forty-nine contemporaneous patients served as controls. Primary graft dysfunction grade 3 at 72 hours (PGD3-72 hours) was higher in the CLES group with 16 (24%) vs 2 (4%) in the control (common RD 95% CI, 0.07-0.32; p = 0.0009). All recipients survived to 30 days and 1-year survival was similar for both groups (92% controls vs 89% CLES; common RD 95% CI, -0.14-0.08; p = 0.58). Total preservation time, hospital and ICU lengths of stay, and time to first extubation were longer in the CLES group. CONCLUSIONS: Remote ex vivo perfusion of lung allografts declined for conventional transplantation at a dedicated CLES facility is feasible and resulted in additional transplants. Recipients of allografts assessed with a CLES had a higher rate of PGD3-72 hours, but similar 30-day and 1-year outcomes compared to conventional lung recipients. (NCT02234128).

Long-term evaluation of the safety and efficacy of recombinant human pentraxin-2 (rhPTX-2) in patients with idiopathic pulmonary fibrosis (IPF): an open-label extension study.

BACKGROUND: Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151-202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks. METHODS: Patients who completed the randomized PRM-151-202 study period were eligible for the OLE, during which all patients received rhPTX-2, having started rhPTX-2 (i.e., crossed from placebo) or continued rhPTX-2 after Week 28. rhPTX-2 was administered in 28-week cycles, with 10 mg/kg intravenous infusions (60 min) on Days 1, 3, and 5 in the first week of each cycle, then one infusion every 4 weeks up to Week 128. The OLE primary objective was to assess the long-term safety and tolerability of rhPTX-2. Other outcomes included FVC, 6MWD, and patient-reported outcomes (descriptive analysis). RESULTS: All 111 patients who completed the randomized period entered the OLE (n = 37 started rhPTX-2; n = 74 continued rhPTX-2); 57 (51.4%) completed to Week 128. The treatment-emergent adverse event (TEAE) profile was consistent with the randomized period, with the majority of TEAEs graded mild or moderate. Serious TEAEs occurred in 47 patients (42.3%), most frequently IPF (n = 11; 9.9%), pneumonia (n = 7; 6.3%), and acute respiratory failure (n = 3; 2.7%). Three patients underwent lung transplantation. Most serious TEAEs (and all 14 fatal events) were considered unrelated to rhPTX-2 treatment. For patients starting vs continuing rhPTX-2, mean (95% confidence interval) changes from baseline to Week 128 were, respectively, - 6.2% (- 7.7; - 4.6) and - 5.7% (- 8.0; - 3.3) for percent predicted FVC and - 36.3 m (- 65.8; - 6.9) and - 28.9 m (- 54.3; - 3.6) for 6MWD; however, conclusions were limited by patient numbers at Week 128. CONCLUSIONS: Long-term treatment (up to 128 weeks) with rhPTX-2 was well tolerated in patients with IPF, with no new safety signals emerging in the OLE. The limited efficacy data over 128 weeks may suggest a trend towards a treatment effect. Trial registration NCT02550873; EudraCT 2014-004782-24.

Ex Vivo Lung Perfusion: A Review of Current and Future Application in Lung Transplantation.

The number of waitlisted lung transplant candidates exceeds the availability of donor organs. Barriers to utilization of donor lungs include suboptimal lung allograft function, long ischemic times due to geographical distance between donor and recipient, and a wide array of other logistical and medical challenges. Ex vivo lung perfusion (EVLP) is a modality that allows donor lungs to be evaluated in a closed circuit outside of the body and extends lung donor assessment prior to final acceptance for transplantation. EVLP was first utilized successfully in 2001 in Lund, Sweden. Since its initial use, EVLP has facilitated hundreds of lung transplants that would not have otherwise happened. EVLP technology continues to evolve and improve, and currently there are multiple commercially available systems, and more under investigation worldwide. Although barriers to universal utilization of EVLP exist, the possibility for more widespread adaptation of this technology abounds. Not only does EVLP have diagnostic capabilities as an organ monitoring device but also the therapeutic potential to improve lung allograft quality when specific issues are encountered. Expanded treatment potential includes the use of immunomodulatory treatment to reduce primary graft dysfunction, as well as targeted antimicrobial therapy to treat infection. In this review, we will highlight the historical development, the current state of utilization/capability, and the future promise of this technology.

Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response, and immunothrombosis. Fostamatinib is a novel spleen tyrosine kinase inhibitor that we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with COVID-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. RESULTS: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared with 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ±â€…0.3 vs -2.6 ±â€…0.4, P = .035) and the median length in the intensive care unit was 3 days in the fostamatinib group vs 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs 28, P = .027). There were trends toward more rapid reductions in C-reactive protein, D-dimer, fibrinogen, and ferritin levels in the fostamatinib group. CONCLUSION: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared with placebo. These results warrant further validation in larger confirmatory trials. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov, NCT04579393.

Inhaled Nitric Oxide via High-Flow Nasal Cannula in Patients with Acute Respiratory Failure Related to COVID-19.

INTRODUCTION: Limited evidence exists regarding use of inhaled nitric oxide (iNO) in spontaneously breathing patients. We evaluated the effectiveness of continuous iNO via high-flow nasal cannula (HFNC) in COVID-19 respiratory failure. METHODS: We performed a multicenter cohort study of patients with respiratory failure from COVID-19 managed with HFNC. Patients were stratified by administration of iNO via HFNC. Regression analysis was used to compare the need for mechanical ventilation and secondary endpoints including hospital mortality, length of stay, acute kidney injury, need for renal replacement therapy, and need for extracorporeal life support. RESULTS: A total of 272 patients were identified and 66 (24.3%) of these patients received iNO via HFNC for a median of 88 h (interquartile range: 44, 135). After 12 h of iNO, supplemental oxygen requirement was unchanged or increased in 52.7% of patients. Twenty-nine (43.9%) patients treated with iNO compared to 79 (38.3%) patients without iNO therapy required endotracheal intubation (P = .47). After multivariable adjustment, there was no difference in need for mechanical ventilation between groups (odds ratio: 1.53; 95% confidence interval [CI]: 0.74-3.17), however, iNO administration was associated with longer hospital length of stay (incidence rate ratio: 1.41; 95% CI: 1.31-1.51). No difference was found for mortality, acute kidney injury, need for renal replacement therapy, or need for extracorporeal life support. CONCLUSION: In patients with COVID-19 respiratory failure, iNO delivered via HFNC did not reduce oxygen requirements in the majority of patients or improve clinical outcomes. Given the observed association with increased length of stay, judicious selection of those likely to benefit from this therapy is warranted.

Donor derived cell free DNA% is elevated with pathogens that are risk factors for acute and chronic lung allograft injury.

BACKGROUND: Acute and chronic forms of lung allograft injury are associated with specific respiratory pathogens. Donor-derived cell free DNA (ddcfDNA) has been shown to be elevated with acute lung allograft injury and predictive of long-term outcomes. We examined the %ddcfDNA values at times of microbial isolation from bronchoalveolar lavage (BAL). METHODS: Two hundred and six BAL samples from 51 Lung Transplant Recipients (LTRs) with concurrently available plasma %ddcfDNA were analyzed along with microbiology and histopathology. Microbial species were grouped into bacterial, fungal, and viral and "higher risk" and "lower risk" cohorts based on historical association with downstream allograft dysfunction. Analyses were performed to determine pathogen category association with %ddcfDNA, independent of inter-subject variability. RESULTS: Presence of microbial isolates in BAL was not associated with elevated %ddcfDNA compared to samples without isolates. However, "higher risk" bacterial and viral microbes showed greater %ddcfDNA values than lower risk species (1.19% vs. 0.65%, p < 0.01), independent of inter-subject variability. Histopathologic abnormalities concurrent with pathogen isolation were associated with higher %ddcfDNA compared to isolation episodes with normal histopathology (medians 1.23% and 0.66%, p = 0.05). Assessments showed no evidence of correlation between histopathology or bronchoscopy indication and presence of higher risk vs. lower risk pathogens. CONCLUSION: %ddcfDNA is higher among cases of microbial isolation with concurrent abnormal histopathology and with isolation of higher risk pathogens known to increase risk of allograft dysfunction. Future studies should assess if %ddcfDNA can be used to stratify pathogens for risk of CLAD and identify pathogen associated injury prior to histopathology.

Incidence and prognostic significance of pleural effusions in pulmonary arterial hypertension.

It has been suggested pleural effusions may develop in right heart failure in the absence of left heart disease. The incidence and prognostic significance of pleural effusions in pulmonary arterial hypertension is uncertain. Patients with pulmonary arterial hypertension followed at our tertiary care center were reviewed. Survival was examined based on the subsequent development of a pleural effusion. A total of 191 patients with pulmonary arterial hypertension met the inclusion criteria. The prevalence of pleural effusions on initial assessment was 7.3%. Among patients without a pleural effusion on initial imaging and at least one follow-up computerized tomography (N = 142), pleural effusion developed in 27.5% (N = 39) of patients. No alternative etiology of the effusion was identified in 19 (48.7%) cases and effusions deemed related to pulmonary arterial hypertension occurred at an incident rate of 38.6 cases per 1000 person-years. Of these, 14 (73.7%) were bilateral, 3 (15.8%) were right-sided, and 2 (10.5%) were left-sided. Effusion size was trace or small in 18 patients (94.7%). Development of a new pleural effusion was associated with attenuated survival in unadjusted survival analysis (HR: 3.80; 95% CI: 1.55-9.31), multivariate analysis (HR: 5.13; 95% CI: 1.86-14.16), and after the multivariate model was adjusted for concomitant pericardial effusion (HR: 4.86; 95% CI: 1.51-15.71). Negative impact on survival remained unchanged when effusions more likely related to an alternative cause were removed from analysis. In conclusion, pleural effusions can complicate pulmonary arterial hypertension in the absence of left heart disease. These effusions are frequently small in size, bilateral in location, and their presence is associated with decreased survival. Attenuated survival appears independent of the risk associated with a new pericardial effusion.

Development and Validation of a Clinical Diagnostic Scoring System for the Diagnosis of Idiopathic Pulmonary Fibrosis.

Rationale: Interpreting the radiologic data in conjunction with an objective clinical score could help to harmonize idiopathic pulmonary fibrosis (IPF) diagnosis and improve accuracy. Objectives: We sought to establish and validate a multivariable objective scoring model based on clinical parameters by stratifying the risk of patients having IPF diagnosed versus having other forms of interstitial lung disease (ILD) diagnosis. Methods: A clinical score was derived from review of patients evaluated at the Inova Fairfax ILD Program and validated in three distinct cohorts. On the basis of known IPF clinical characteristics, a multivariable model was created and assessed by using receiver operating characteristic curves. Results: There were 844 patients with ILD with either IPF (n = 347, 41%) or non-IPF ILD (n = 497, 59%) diagnosis. On the basis of calculated odds ratios, a score was assigned to each of the following clinical parameters: age, sex, smoking history, race or ethnicity, ILD family history, exposures, presence of connective tissue disease signs or symptoms, and velcro crackles. The final Fairfax IPF Clinical Score (FICS) ranged from 1 to 25. The clinical diagnostic score system was accurate in predicting IPF, as measured by the area under the curve (0.88) in the derivation cohort, with similar areas under the curve of 0.91, 0.81, and 0.71 being demonstrated in the respective validation cohorts. Conclusions: The FICS appears to be an accurate tool for estimating the pretest probability of IPF in patients with ILD. How the FICS performs in conjunction with the various high-resolution computed tomographic patterns remains to be determined. This model could ultimately be useful for increasing the degree of confidence in the final diagnosis and could help to obviate the need for lung biopsy in cases with non-usual interstitial pneumonia patterns on high-resolution computed tomographic images.

Idiopathic pulmonary fibrosis patients with severe physiologic impairment: characteristics and outcomes.

RESEARCH QUESTION: There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment. PATIENTS AND METHODS: IPF patients with severe physiologic impairment defined by FVC ≤ 50% and/or DLco ≤ 30% predicted evaluated in the Inova Advanced Lung Disease Program between 2011 and 2019 were included. Demographic, physiologic, functional treatment and outcome data were collated. RESULTS: There were 531 patients with IPF evaluated of whom 242 (46%) had severe physiologic impairment. Mean age was 72 ± 8 years; baseline FVC was 53 ± 17% and DLCO 28 ± 9% of predicted. The mean 6 min walks test (6MWT) distance was 304 ± 121 m with 59% of the patients requiring supplemental oxygen ([Formula: see text] group). There was a poor correlation between the 6MWT distance and both FVC% and DLco%. Patients in the 6MWTRA group had a better transplant-free survival than the [Formula: see text] group (p = 0.002). Patients managed before October 2014 and not receiving antifibrotic therapy had worse outcomes with reduced transplant-free survival compared with patients presenting after this date who did receive antifibrotic therapy (n = 113) (log rank p < 0.0001). CONCLUSION: IPF patients often present with severe physiologic impairment which may be poorly correlated with their functional status. Assessment of IPF disease severity should not be based on physiologic impairment alone, but should also encompass functional status as well as need for supplemental oxygen. Antifibrotic therapy in patients with severe physiologic impairment is associated with improved outcomes.

Association Between Anticoagulation and Survival in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation Patient Registry.

BACKGROUND: Aberrations in the coagulation system have been implicated in the pathogenesis of interstitial lung disease (ILD). Anticoagulants have been proposed as a potential therapy in ILD; however, a randomized controlled trial examining warfarin as a treatment for IPF was terminated early due to increased death rates. This has led some to speculate that warfarin specifically may be harmful in ILD, and use of direct oral anticoagulants (DOACs) could result in superior outcomes. RESEARCH QUESTION: The goal of this study was to delineate the relationship between anticoagulation and outcomes in patients with ILD through an analysis of the Pulmonary Fibrosis Foundation Patient Registry. STUDY DESIGN AND METHODS: An analysis of all patients in the Pulmonary Fibrosis Foundation Patient Registry was performed. Patients were stratified into three groups: no anticoagulation, DOAC use, or warfarin use. Survival was analyzed by using both Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 1,911 patients included in the analysis, 174 (9.1%) were given anticoagulants; 93 (4.9%) received DOACs, and 81 (4.2%) received warfarin. There was a twofold increased risk of death or transplant for patients receiving DOACS; for warfarin, the risk was over two and half times greater. DOACs were not associated with an increased risk of mortality following adjustment for confounding variables. However, even after adjustment, patients given the anticoagulant warfarin remained at increased risk of mortality. In patients with IPF, warfarin was associated with reduced transplant-free survival, but DOACs were not. There was no statistically significant difference in survival between those receiving warfarin and those receiving a DOAC. INTERPRETATION: The need for anticoagulation is associated with an increased risk for death or transplant in patients with ILD, in both the IPF and non-IPF population. Further research is required to determine if warfarin and DOACs present varying safety profiles in patients with ILD.

Surgical Lung Biopsy for Interstitial Lung Disease. Safety and Feasibility at a Tertiary Referral Center.

Rationale: Video-assisted thoracoscopic surgery (VATS) remains the gold standard for interstitial lung disease (ILD) characterization when histology is deemed necessary. There is diminishing use of VATS owing to increased reliance on high-resolution computed tomographic patterns, as well as concerns regarding the potential morbidity and mortality of the procedure.Objectives: The goal of this study was to evaluate the safety and tolerability of VATS among a broad group of patients with ILD referred to a tertiary care center.Methods: Data for all patients with ILD who underwent VATS lung biopsies at Inova Fairfax hospital for the period from December 2012 to September 2019 were collected. Clinical, physiologic, and functional parameters as well as postoperative outcomes including any complications, hospital length of stay, and mortality were collated.Results: There were 268 diagnostic VATS biopsies performed during the period. The mean age of the cohort was 63 ± 13 years, 54% were male, and 25% were ultimately diagnosed with idiopathic pulmonary fibrosis. Two hundred twenty-nine patients were scheduled (85%, Elective VATS group) whereas 39 were inpatients (15%). In the elective group, the 1-month complication rate was 8%, whereas 4% had a severe complication, and there were no deaths. The only mortalities were in the group who were hospitalized before the VATS (4/39 = 10%). Complications were less frequent when VATS was requested by the tertiary referral ILD team. Of the elective group, 87% patients were discharged the same day.Conclusions: This report demonstrates the safety, tolerability, and feasibility of VATS lung biopsy as a same-day procedure in the modern era, especially if patients are first vetted by a team with expertise in the field of ILD. These results support a lower threshold to pursue a VATS biopsy when histology is required for an ILD diagnosis.