Diagnostic delay in pulmonary arterial hypertension: Insights from the Australian and New Zealand pulmonary hypertension registry.

BACKGROUND AND OBJECTIVE: Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients. METHODS: A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression. RESULTS: A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival. CONCLUSION: PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval.

Socioeconomic deprivation is not associated with reduced survival of lung transplant recipients.

BACKGROUND: Important risk factors for long-term survival of lung transplant (LT) recipients are infection, acute graft rejection (AR) and chronic lung allograft dysfunction (CLAD). Socioeconomic deprivation (SED) is associated with increased graft failure rate after heart and kidney transplantation, but has not been investigated in LT recipients. The aim of this study was to evaluate an association between LT recipients' SED status and development of AR, CLAD, and long-term survival. METHODS: This was a retrospective cohort study. Over a 23 y period, 233 patients were identified from the Auckland City Hospital Lung Transplant Registry, Auckland, New Zealand. All patients were divided into two groups according to the 2013 New Zealand Deprivation Index Score. RESULTS: The incidence of AR in the higher SED group was 34.0/100 person-y (95% confidence interval [CI]: 24.7-46.7/100 person-y) and in the lower SED group 40.2/100 person-y (95% CI: 33.5-48.3/100 person-y) (P = 0.373). The incidence of CLAD in the higher SED group was 10.7/100 person-y (95% CI: 6.2-18.4/100 person-y) and 9.3 (6.9-12.5/100 person-y) in the lower SED group (P = 0.645). Mortality in the higher SED group was 12.9/100 person-y (95% CI: 9.2-17.9/100 person-y) and 12.4/100 person-y (95% CI: 10.0-15.3/100 person-y) in the lower SED group (P = 0.834). CONCLUSIONS: SED status of LT recipients in New Zealand has no negative effect on development of AR, CLAD, and patients' survival.

Interstitial pneumonitis associated with sirolimus: a dilemma for lung transplantation.

Rapamycin/sirolimus (SR), trade named Rapammune (Wyeth-Ayerst, Sydney, Australia), is a potent immunosuppressive drug associated with myelosuppression, hypertension, hyperlipidemia, and infection. Rapamycin/sirolimus-induced pneumonitis has been described previously in renal transplant recipients, and this report describes a stable heart-lung transplant recipient who developed a pulmonary infiltrate that reversed after ceasing SR therapy. We believe that immunosuppression-induced pneumonitis in a lung allograft is a serious dilemma for lung transplant physicians

Surveillance bronchoscopy in lung transplant recipients: risk versus benefit.

BACKGROUND: Long-term survival of lung transplant (LT) recipients is limited by the development of the bronchiolitis obliterans syndrome (BOS). A number of risk factors for BOS have been identified, which can be detected using bronchoscopy with transbronchial biopsy (TBB). Many LT units perform routine surveillance bronchoscopy (SB) to detect problems such as: acute rejection (AR); infection, particularly with cytomegalovirus (CMV); and lymphocytic bronchiolitis. This study aimed to assess the safety and efficacy of surveillance bronchoscopy in lung transplant recipients (LTRs), including TBB and bronchoalveolar lavage (BAL). METHODS: All bronchoscopy procedures, including SB and clinically indicated (CB) procedures performed on LTRs in one calendar year, were audited prospectively. Complications and clinical utility were recorded to determine the clinical utility both early (3 months and 3 to 12 months) and late (>12 months) post-LT. RESULTS: In one calendar year, 353 procedures (232 SBs and 121 CBs) were performed on 124 LTRs, with 246 performed <1 year post-LT. The complication rates were similar to those reported previously, except for an increased rate of sedation-related complications, particularly up to 3 months post-LT. SBs showed high rates of acute rejection, particularly in the first year post-LT (p = 0.01). The rate of asymptomatic infection diagnosed on BAL remained high regardless of time post-transplant. CONCLUSIONS: This study confirms that SB can frequently detect clinically significant infection and rejection with very low complication rates. The data support SB with TBB up to 12 months post-LT, and ongoing use of SB with BAL (only) to detect clinically silent infection beyond 1 year post-LT.