Repeat Pulmonary Function Testing Research Articles

Bleomycin Affects Lung Function for at Least 5 Years after Treatment for Hodgkin Lymphoma - Data from the International, Randomised Phase 3 Rathl Trial

Introduction: Bleomycin has been an integral part of classical Hodgkin lymphoma (HL) treatment for decades but carries significant toxicity. In particular, acute bleomycin-related lung toxicity occurs in a minority of patients (pts) but has mortality rates as high as 25%. The long-term effects of bleomycin in HL and its impact on lung function are not well known and there is no established guidance for lung screening. The aim of this analysis was to evaluate the impact of bleomycin dose on lung function up to 5 years after treatment in pts recruited to the international, phase 3 RATHL trial. Methods: RATHL recruited pts with intermediate- or advanced-stage HL aged ≥18 years. Pts received 2 cycles of standard ABVD followed by PET assessment. Pts with complete metabolic response (CMR) received 4 further cycles of chemotherapy, with (ABVD arm; n=469) or without (AVD arm; n=464) bleomycin (12 or 4 doses bleomycin in total, respectively). PET-positive pts switched to BEACOPP-based treatment (total 8-10 doses bleomycin; n=172). Pulmonary function tests (PFTs) were performed at baseline, end of treatment (EOT) and annually for 5 years. Linear regression was used to assess changes in DLCO from baseline and Cox regression used to assess the time to return to within 10% of baseline values, censoring at relapse or death, in all pts, and those with a more than 10% reduction at EOT. Results: Median age was 33 years (range 18 - 79), 8.2% were aged >60 and 15.1% had a pre-existing respiratory disorder, including asthma in 8.4%. In pts with available data, 18.2% were smokers and 22.2% were ex-smokers with a median of 10 pack-years (IQR: 4 - 20). Baseline DLCO values were low (<75%) in 339 (29.8%) pts and were influenced by disease burden, with lower median DLCO in pts with mediastinal bulk (79%, IQR: 69.0 - 89.4) than in those without (83.1% (73- 94), p=0.006). Grade ≥3 respiratory adverse events occurred more frequently in the ABVD arm (17 events; 3.6%) than with AVD (7 events; 1.5%), p = 0.041. There was one respiratory death (pulmonary fibrosis) in the ABVD arm. PFT data were available for 779 pts at EOT, 386 pts at 2-year follow up and 196 pts at 5 years; uptake of repeat PFT was unaffected by treatment arm or presence of prior abnormal results. Changes in DLCO adjusted to baseline values for randomised patients are shown in the Figure. Pts randomised to AVD had a significantly smaller reduction in DLCO at EOT compared to those given ABVD or escalated to BEACOPP: +4.1% (95%CI: 1.8 to 6.5, p = 0.001 and +4.1 (0.1 to 8.0) p = 0.043). Other factors associated with a reduction in DLCO were age (-1.6% (-2.4 to -0.8) for a 10-year increase, p<0.001), female sex (-2.7% (-5.0 to -0.44), p=0.019) and baseline pulmonary disease (-4.9 (-8.4 to -1.4), p = 0.006). There was no evidence of an association with abnormal baseline DLCO values. DLCO had reduced to <90% of baseline values for 247 pts (59.8%) in the ABVD arm compared with 167 pts (40.6%; p<0.001) with AVD, and 63 (53.1%) with BEACOPP. At 2 years after EOT, DLCO had recovered to within 90% of baseline for 69.6% (95% CI: 64.9 - 74.1) of pts in the ABVD arm, 81.4% (77.4 - 85.2) with AVD and 68.5% (59.8 - 76.9) with BEACOPP. DLCO values remained <90% of baseline for 136 pts during follow-up with no reported recovery, with a median PFT follow-up of 18.3 months (IQR: 6.4 - 42.7) after registration. 58 pts had persistent reductions in DLCO at ≥2-year follow up (35 ABVD arm, 10 AVD; 13 BEACOPP arm). Factors associated with a slower recovery of DLCO on univariable analysis were treatment on the ABVD arm (HR 0.71, 95% CI: 0.57 - 0.90; p=0.004 compared with AVD), history of pulmonary disease (HR 0.66 (0.46 - 0.95; p=0.023) and female sex (HR 1.25, 1.01 - 1.54; p=0.041). DLCO values were consistently higher in the AVD arm than with ABVD throughout follow-up with a mean difference of 3.2% (95% CI: 0.3 to 6.1; p=0.029) at 2 years and 5.0% (1.20 to 8.8; p=0.010) at 5 years, after adjustment for baseline DLCO values (see Figure). Findings were consistent after excluding the minority of pts that received radiotherapy. Conclusions: Baseline RFTs are influenced by disease burden and do not predict subsequent bleomycin-related changes in lung function. Whilst individual grade ≥3 events were uncommon, there was a population-wide reduction in diffusion capacity that was only partially reversible at 5 years, findings that might have clinical consequences in later years for pts cured of HL. These data strongly support efforts to minimise bleomycin use in the treatment of HL.

Impact of COVID infection on lung function test and quality of life

Post-COVID-19 pulmonary sequalae are well-recognized early in the pandemic. Survivorship clinics are crucial for managing at-risk patients. However, it is unclear who requires pulmonary function test (PFT) and when PFTs should be performed. We aim to investigate for whom and how these interval PFTs should be performed. We performed a single-centre, prospective cohort study on COVID-19 survivors between 1st May 2020 and 31st April 2022. These patients were followed up at 6, 9 and 12 months with interval PFT and Short Form-36 (SF-36) Health Survey. Those with PFT defects were offered a computed tomography scan of the thorax. Of the 46 patients recruited, 17 (37%) had severe/critical illness. Compared to those with mild/moderate disease, these patients were more likely to experience DLCO defects (59% versus 17%, p = 0.005) and had lower SF-36 scores (mean physical component summary score of 45 ± 12 versus 52 ± 8, p = 0.046). These differences were most notable at 6 months, compared to the 9- and 12-months intervals. DLCO defects were also associated with older age, raised inflammatory markers and extensive CXR infiltrates. Besides interstitial-like abnormalities, obesity and undiagnosed lung conditions accounted for 39% of the PFT abnormalities. Interval PFTs can be performed earliest 6 months post-COVID-19. Patients with normal tests were unlikely to develop new abnormalities and would not require repeat PFTs. Abnormal PFTs can be followed-up with repeat PFTs 6 monthly until resolution. Non-COVID-19 differentials should be considered for persistent PFT abnormalities.

1023 A Case of Stridor in the Sleep Clinic

Abstract Introduction Multisystem atrophy (MSA) is a neurological degenerative progressive disease affecting multiple systems. These patients are frequently seen in the sleep clinic at specialty centers by sleep neurologists for co-management of sleep disordered breathing and nocturnal respiratory issues. Stridor is a life-threatening condition seen in these patients and requires emergent action. We present a case of MSA with worsening stridor that was missed in the era of virtual telemedicine. Report of case(s) A 53-year-old female with a history of obstructive sleep apnea (OSA) on BiPAP S and multiple system atrophy with parkinsonian subtype presented virtually to sleep clinic for follow up evaluation of her sleep disordered breathing. Six months prior to her visit she was noted to have bilateral vocal fold hypomobility without stridor. At that time, she had a residual apnea-hypopnea index (AHI) of 1.4 with BiPAP-S 16/13 cm H2O and no nocturnal stridor. She was wheelchair bound. She had routine follow up visits with various providers however these were telemedicine visits with her husband doing most of the talking due to weakness. Over the next 5 months she had worsening fatigue and was using BiPAP S during the day intermittently and was referred to the sleep medicine clinic for consideration of supplemental oxygen at night. A repeat overnight oximetry revealed residual oxygen desaturation index (ODI) of 2.5/hr while on BiPAP S. Repeat pulmonary function testing was ordered and patient was recommended to return for immediate in person follow up. When seen in person, patient was noted to have significant stridor which had been ongoing and worsening over last few months including being appreciated while on PAP therapy. Emergent same-day ENT consultation was arranged by sleep providers. Posterior cordectomy was performed shortly thereafter. The patient was scheduled for an AVAPS titration study. Conclusion In cases with progressive neuromuscular disease, stridor may be missed during virtual appointments for a variety of reasons including technical difficulties, or the virtual medium not being sensitive enough to convey stridor. This case highlights the importance of having a high index of suspicion for stridor and impending respiratory failure requiring emergent intervention in patients with neuromuscular disease. Support (if any)

A CASE OF LOMUSTINE-INDUCED PNEUMONITIS

A CASE OF LOMUSTINE-INDUCED PNEUMONITIS

INTRIGUING LUNG FUNCTION TESTS IN NEUROMUSCULAR WEAKNESS

INTRIGUING LUNG FUNCTION TESTS IN NEUROMUSCULAR WEAKNESS

Postinduction therapy pulmonary function retesting is necessary before surgical resection for non–small cell lung cancer

ObjectivePretreatment-predicted postoperative diffusing capacity of the lung for carbon monoxide (DLCO) has been associated with operative mortality in patients who receive induction therapy for resectable non–small cell lung cancer (NSCLC). It is unknown whether a reduction in pulmonary function after induction therapy and before surgery affects the risk of morbidity or mortality. We sought to determine the relationship between induction therapy and perioperative outcomes as a function of postinduction pulmonary status in patients who underwent surgical resection for NSCLC. MethodsWe retrospectively reviewed data for 1001 patients with pathologic stage I, II, or III NSCLC who received induction therapy before lung resection. Pulmonary function was defined according to American College of Surgeons Oncology Group major criteria: DLCO ≥50% = normal; DLCO <50% = impaired. Patients were categorized into 5 subgroups according to combined pre- and postinduction DLCO status: normal-normal, normal-impaired, impaired-normal, impaired-impaired, and preinduction only (without postinduction pulmonary function test measurements). Multivariable logistic regression was used to quantify the relationship between DLCO categories and dichotomous end points. ResultsIn multivariable analysis, normal-impaired DLCO status was associated with an increased risk of respiratory complications (odds ratio, 2.29 [95% CI, 1.12-4.49]; P = .02) and in-hospital complications (odds ratio, 2.83 [95% CI, 1.55-5.26]; P < .001). Type of neoadjuvant therapy was not associated with an increased risk of complications, compared with conventional chemotherapy. ConclusionsReduced postinduction DLCO might predict perioperative outcomes. The use of repeat pulmonary function testing might identify patients at higher risk of morbidity or mortality.

PRIMARY PULMONARY NODULAR AMYLOIDOSIS IN A FEMALE WITH UNDIAGNOSED SJOGREN'S SYNDROME

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Pulmonary amyloidosis is characterized by extracellular deposition of insoluble, misfolded fibrils within the lung. Isolated pulmonary amyloidosis is a rare condition especially in association with Sjogren’s syndrome. Frequently asymptomatic, we report a case of nodular pulmonary amyloidosis in a young, Hispanic female who presented with dyspnea. CASE PRESENTATION: A 45 year-old female presented with shortness of breath and chest tightness for 3 years. Her symptoms progressed in frequency, functional status deteriorated and she experienced a 20-pound weight loss in the past year. Initial imaging 2 years prior revealed multiple lung nodules with a thin-walled cyst in the right middle lobe (RML). Quantiferon-TB Gold and coccidioidomycosis serology was negative. Pulmonary function testing (PFT) demonstrated a minimal obstructive lung defect with mild response to bronchodilator. Repeat imaging demonstrating increasing size of multiple pulmonary nodules, a now solid nodule of RML, and a 2.6 cm left suprasternal lymph node. Computed tomography (CT)-guided biopsy revealed nodular pulmonary amyloidosis confirmed with congo red stain. The patient was placed on a prednisone taper with improvement of symptoms. She continued to endorse multiple recurring subcutaneous nodules of both upper and lower extremities, dry mouth, dry eyes, cold fingers, and hair loss. Lab studies were notable for positive anti-SSA/Ro antibodies and rheumatoid factor (208 IU/mL), and negative cyclic citrullinated peptide antibody and antinuclear antibody. Serum protein electrophoresis identified a mild elevation of gamma globulins. Plaquenil, Rituximab and Methotrexate therapy was initiated. Repeat PFT had normal spirometry, lung volume and diffusion capacity. DISCUSSION: Pulmonary amyloidosis appears in three forms: pulmonary nodules, tracheobronchial, and diffuse alveolar septal. Nodular pulmonary amyloidosis is often an incidental finding and is indistinguishable from neoplasm or granulomatous lesions. Nodules are slowly enlarging and may cavitate or calcify. Histological examination is necessary to determine the diagnosis. In this case, untreated Sjögren’s syndrome with gammaglobinemia likely led to deposition of amyloid in lung. In literature, PFT are mostly normal with a small subset demonstrating restrictive pattern and even fewer with reduced diffusion. Our patient initially presented with obstructive pattern likely due to the large cyst compromising elastic recoil of the lungs. CONCLUSIONS: In primary nodular pulmonary amyloidosis, nodules are radiographically nonspecific and require biopsy for diagnosis. Amyloidosis should be included in the differential diagnosis of multiple pulmomary nodules. Management is not well defined due to the low incidence of the disease. When associated with Sjögren’s syndrome, there is reported success with treatment of steroids and immunosuppression. Reference #1: Xian, Jonathan Z. et all. "A 45-Year-Old Woman With Multiple Pulmonary Nodules and Sjogren Syndrome.” CHEST 2019;155(2):e51-154. Reference #2: Heraganahally, Subash et all. "Pulmonary AL - amyloidosis masquerading as lung malignancy in an Australian Indigenous patient with Sjogren's syndrome.” Respiratory Medicine Case Reports 2019;26:94-97 Reference #3: Garcia-Sanchez, Aldara et all. "Amyloidosis as a Cause of Cystic Pulmonary Fibrosis Associated With Pulmonary Nodules.” Arch Bronconeumol 2018;54(9): 481-494. DISCLOSURES: No relevant relationships by Aarti Mittal, source=Web Response No relevant relationships by Erin Wiltchik, source=Web Response

27. A new presentation of interstitial lung disease

27. A new presentation of interstitial lung disease

5. Isolated head drop: first symptom of anti-synthetase syndrome

IntroductionHead drop is an unusual clinical manifestation of myositis or neuromuscular weakness, and typically requires extensive investigation to identify the underlying pathology. Case report data are limited on this topic.Case descriptionA 72-year-old man with a background of extractable nuclear antigen (ENA) negative mixed connective tissue disease, trigeminal neuralgia, interstitial nephritis and ischaemic heart disease presented with an isolated head drop. On further prompting, he confirmed mild shortness of breath on exertion. He had sclerodactyly but no features of mechanic’s hands. Serum creatinine kinase was 1398 IU/L. Electromyography was myelopathic. Muscle biopsy taken from the neck was inconclusive. He had a strongly positive anti-nuclear antibody (ANA) test, and borderline myositis ENA panel result with borderline positive anti-EJ antibody.The myositis panel result prompted further investigation for underlying interstitial lung disease. Pulmonary function testing revealed a restrictive picture, with KCO of 82%. High resolution computed tomography showed areas of fine interstitial fibrotic change in all lobes.He was treated with a reducing course of oral prednisolone and 15mg weekly oral methotrexate with an excellent clinical response, with resolution of the head drop and normalisation of serum CK value. Repeat pulmonary function testing remains stable after 5 months.DiscussionThis is an unusual presentation of presumed anti-synthetase syndrome. As methotrexate had already been prescribed before the underlying lung pathology was identified with resulting excellent clinical response and stable respiratory symptoms, a multi-disciplinary decision was made to continue with this choice of disease modifying agent. The decision to use methotrexate in the presence of interstitial fibrosis is always difficult, and requires close liaison between rheumatology and respiratory colleagues.Key learning pointsPositive anti-synthetase antibodies should prompt further investigation for underlying interstitial lung disease. Head drop can be a first symptom of autoimmune myositis and warrants further investigation.Conflicts of interestThe authors have declared no conflicts of interest.

INTERSTITIAL LUNG DISEASE IN AN ELDERLY MAN WITH GIANT CELL ARTERITIS

PURPOSE: To describe the association of interstitial lung disease (ILD) with giant cell arteritis (GCA). METHODS: Case report RESULTS: An 89-year-old never-smoker male with a history of polymyalgia rheumatica (PMR) on chronic low dose prednisone was later diagnosed with giant cell arteritis (GCA) confirmed by temporal artery biopsy. At the time of GCA diagnosis, the patient reported dyspnea and chest radiographs showed bilateral interstitial infiltrate with peripheral and basilar predominance. Chest computed-tomography (CT) performed several months later showed findings of a fibrosing interstitial pneumonia with mild traction bronchiectasis involving predominantly the bibasilar and peripheral lung zones, consistent with a probable usual interstitial pneumonia (UIP) pattern (Figure A). These findings were new compared to prior CT imaging four years before. Pulmonary function test (PFT) revealed a moderate restrictive pattern with forced vital capacity (FVC) 73% and diffusing capacity of the lungs for carbon monoxide (DLCO) 53%. The patient experienced improvement with increased prednisone dose. At follow up 6 months after hospitalization, repeat PFT revealed FVC 91% and DLCO 65%. Repeat chest CT showed that parenchymal infiltrates improved with decreased reticulation and resolution of ground-glass opacities (Figure B). CONCLUSIONS: The temporal relationship in this case suggests the association of GCA with ILD. Although the CT findings suggested a UIP pattern, the patient experienced improvement with prednisone treatment. CLINICAL IMPLICATIONS: In recent years there have been multiple reports of ILD or pulmonary fibrosis associated with small vessel vasculitis, especially ANCA-related vasculitis. This case suggests large vessel vasculitis may cause ILD and mimic idiopathic pulmonary fibrosis in the elderly.

Gender difference on the knowledge, attitude, and practice of COPD diagnosis and treatment: a national, multicenter, cross-sectional survey in China.

PurposeTo investigate the gender difference in knowledge, attitude, and practice of COPD diagnosis and treatment in China.Patients and methodsA nationwide, multicenter, cross-sectional questionnaire study was carried out to investigate patients’ understanding and experience of COPD between September 2007 and December 2008.ResultsTwo thousand and seventy-two patients were recruited from eleven centers. The final effective questionnaires were those of 1,698 cases, of which 32% were female. Women were younger, had higher body mass index, were more never smokers, and had lesser pack-years (all P<0.01). More women had under elementary education level and monthly income <1,000 RMB (about 160 USD) (all P<0.01). Women had higher ratio of FEV1/FVC (54.1±10.9 vs 50.2±11.5), FEV1% (50.0±19.1 vs 45.4±29.0), and lower short form-36 mental component summary (57.5±26.8 vs 61.3±25.0) (all P<0.01). Fewer women reported severe exacerbation (defined as an acute worsening of respiratory symptoms that results in patient’s hospitalization) in the previous year (44.5% vs 51.6%, P<0.05). More women reported that they never heard of COPD before (67.0% vs 59.0%, P<0.01). Less women reported that physician had to tell them they had emphysema (50.5% vs 60.4%) or COPD (31.9% vs 37.9%). Less women had pulmonary function test (PFT) done before (65.2% vs 70.4%, P<0.05). More women reported that they would not repeat PFT annually (91.7% vs 87.6%, P<0.05) and did not know the PFT results (78.6% vs 73.1%, P<0.05). More women reported not having had pulmonary rehabilitation before (87.8% vs 83.6%, P<0.05). Fewer women reported knowing that COPD should be given combined therapy (38.3% vs 44.5%) and long-term treatment (46.1% vs 51.9%) (all P<0.05).ConclusionMale and female patients had different experiences on COPD diagnosis and treatment. Physicians should pay more attention to patients’ education on COPD, especially of women.

A RARE ASTHMA MIMIC

SESSION TITLE: Allergy and Airway SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: IgG4 related disease (IgG4-RD) is a recently identified systemic fibro-inflammatory disease associated with elevated circulating levels of IgG4. We are presenting a case of IgG4-RD with hilar mediastinal lymph node and bronchial wall inflammation presenting as an asthma exacerbation. CASE PRESENTATION: A 49 year old male presented to the pulmonary clinic for an evaluation of asthma after several emergency room visits for worsening dyspnea, dry cough and wheezing for 2 months. The patient had no prior history of respiratory issues, and reported that he had never smoked. The patient noted that his facial features appeared to be changing over the previous 4 months. The patient moved from the Democratic Republic of Congo 25 years ago, and currently is a chemistry teacher. The patient reports no recent travel, has no pets. Additionally, the patient denies any recent organic or inorganic fume or dust exposure, and reports no family history of asthma or respiratory issues. Bilateral firm parotid swelling and periorbital edema were prominent on examination making his face appear significantly different from a picture he took 4 months ago. Bilateral wheezes were noted in the lungs with prolonged expiratory phase. The patient’s pulmonary function tests (PFTs) revealed a severe obstructive defect with an FEV1 of 1.33, increased residual volume and a mild diffusion defect. A PET scan was administered to rule out lymphoma as a cause of parotid swelling. Marked enlargement with diffuse hypermetabolic activity was seen in the parotid, submandibular, sublingual, and lacrimal glands. Additionally, multiple mildly hypermetabolic enlarged mediastinal and hilar lymph nodes were observed. There was peribronchial thickening with scattered distal bronchiolar plugging. A biopsy of the submandibular gland revealed sclerosing sialadenitis with interlobular storiform fibrosis, and marked lymphoplasmacytic inflammation. The immunohistochemical findings were consistent with IgG4-RD. A serum IgG subclass analysis was done and showed increased IgG4 level upto 1070mg/dl. The patient was referred to rheumatology and was treated with Rituximab for 3 cycles. His parotid swelling, dysmorphic facial features resolved after the first treatment. So did his dyspnea and wheezing. His repeat PFTs normalized as well. DISCUSSION: IgG-RD is an immune mediated systemic fibro-inflammatory condition that affects almost any organ. Although the inflammation is responsive to steroids, it tends to recur. However, there is a good response to rituximab with less rate of recurrence. CONCLUSIONS: Pulmonary involvement can present as inflammatory pseudo tumors mimicking malignancies, consolidative infiltrates hilar mediastinal lymphadenopathy or bronchovascular inflammation. This patient's symptoms stemmed from bronchovascular inflammation, untreated progression to irreversible bronchovascular fibrosis is highly likely. Reference #1: Clinical Review of Pulmonary Manifestations of IgG4-related DiseaseSabrina N. Campbell, Edmundo Rubio, and A. Lukas LoschnerAnn Am Thorac Soc Vol 2014;11:1466–1475 DISCLOSURES: No relevant relationships by Arezou Khosroshahi, source=Web Response Research support relationship with Boehringer Ingelheim, Sanofi, Fibrogen, Biogen, Please note: >$100000 Added 05/31/2018 by Srihari Veeraraghavan, source=Web Response, value=Grant/Research Support No relevant relationships by Avanthika Wynn, source=Web Response

Systemic Lupus Erythematosus Complicated by Shrinking Lung Syndrome Treated With Belimumab: A Case Report

SESSION TITLE: Inflammatory Diseases Affecting the Lung SESSION TYPE: Student/Resident Case Report Slide PRESENTED ON: Monday, October 24, 2016 at 11:00 AM - 12:00 PM INTRODUCTION: Cardiopulmonary symptoms occur in up to 60% of patients with Systemic Lupus Erythematosus (SLE). Shrinking Lung Syndrome (SLS) is a rare complication of SLE where patients present with restrictive lung disease without imaging findings. We report a case of new onset SLS while receiving hydroxychloroquine, mycophenolate and prednisone treated successfully with belimumab. CASE PRESENTATION: A 44-year old woman with a history of SLE, Lupus Nephritis Class IV-V, presented to the Rheumatology Clinic with dyspnea on exertion. She had recently completed 6 cycles of cyclophosphamide induction therapy for lupus nephritis and was receiving hydroxychloroquine, mycophenolate, and prednisone. Physical examination was unremarkable. SLE Disease Activity Index score was unchanged from the previous visit. Imaging of the chest was perfomed to rule out life threatening conditions. Computerized Tomography Angiography failed to reveal parenchymal pulmonary disease or pulmonary artery filling defects. However, pulmonary function testing (PFT) showed a restrictive pattern with impaired diffusion capacity. To evaluate for diaphragmatic paralysis, seated and supine PFTs were performed which did not show Forced Vital Capacity (FVC) changes in supine position. ECG, echocardiogram and nuclear imaging failed to reveal cardiac causes of dyspnea. Afterwards, the differential diagnosis was narrowed to: SLS, myasthenia gravis, and steroid-induced myopathy. CPK level was slightly increased and anti-acetylcholine receptor antibody was negative. Since the patient had no weakness, myopathy was thought to be unlikely. Belimumab was chosen as a steroid sparing agent. The patient reported resolution of dyspnea after initiating therapy. Her exercise tolerance returned to baseline and repeat PFT showed a persistent restrictive pattern with increased TLC. DISCUSSION: Several hypotheses have tried to explain the findings of SLS but the primary mechanism remains unclear. Our patient developed SLS while undergoing therapy with hydroxychloroquine, mycophenolate and prednisone. Belimumab was used as a steroid sparing therapy. Belimumab, a B Cell Activating Factor, is a new drug in the armamentarium against SLE. The optimal treatment for SLS is not yet determined. Treatment options range from prednisone as first line agent to rituximab as used in some case reports. After treatment with belimumab our patient achieved symptom resolution, increased exercise tolerance, improved VC and TLC. While the mechanism of SLS is poorly understood, B cells likely play a significant role as suggested by positive outcomes with rituximab and belimumab. CONCLUSIONS: Belimumab represents a new weapon against SLE and showed improvement of symptoms and lung volumes after treatment in a patient with SLS. Reference #1: Langenskiöld, E., et al. (2012). Shrinking lung syndrome successfully treated with rituximab and cyclophosphamide. Respiration; International Review of Thoracic Diseases, 84(2), 144-9. http://doi.org/10.1159/000334947 DISCLOSURE: The following authors have nothing to disclose: Felix Reyes, Deana Lazaro No Product/Research Disclosure Information

Clinical Guidelines for the Care of Childhood Cancer Survivors.

The Long-Term Follow-Up Guidelines for survivors of childhood, adolescent, and young adult cancers are evidence- and consensus-based guidelines that have been developed and published by the Children’s Oncology Group (COG) Late Effects Committee, Nursing Discipline, and the Patient Advocacy Committee. Originally published in 2004, the guidelines are currently in version 3.0. While the COG guidelines have been praised as a model for providing risk-based survivorship care, adherence has not been uniform. Reasons for this gap include unawareness on the part of the survivor and/or care team as well as disagreement about the individual recommendations. In some cases, the burden of testing (such as annual echocardiography or repeat pulmonary function testing) may be too great. A small number of intervention studies have documented improved adherence to guideline recommendations with dissemination of informational material. Future studies should focus on individualizing screening recommendations, as well as identifying unnecessary testing.

AB0459 Audit of Methotrexate and Pulmonary Function Tests

BackgroundMethotrexate pneumonitis (MTX-P) is most frequently seen within the first year of treatment1 and is best avoided in established cases of Interstitial Lung disease (ILD). BSR recommends that if pre-treatment...

Supplemental oxygen therapy in bleomycin-induced pulmonary toxicity: REPLY

At the outset, on behalf of all the authors, I thank the reader for having shown keen interest in the article entitled “Reversible Bleomycin Toxicity” published in the July issue of MJAFI.1 The reader has brought out clinically relevant and important issues pertaining to exacerbation/precipitation of bleomycin-induced pulmonary toxicity caused by supplemental oxygen administration particularly in the context of general anaesthesia. As mentioned in our article, exposure to high-dose oxygen is one of the several important risk factors known for development of bleomycin pulmonary toxicity. We did not go into the details of the risk factors of bleomycin toxicity as our article focused mainly on the unusual HRCT features of bleomycin toxicity and imaging (HRCT) demonstration of reversibility of the lesions. I agree with the comments of the reader concerned with regard to the potentially serious synergistic effects of supplemental oxygen therapy in a patient with prior exposure to bleomycin. Exposure to bleomycin appears to sensitise the lungs and potentially fatal acute lung damage can occur at an inspired oxygen concentration which is otherwise considered normal for a healthy individual. However, this issue is debatable.2, 3 Nevertheless, it may be clinically relevant as many of the patients who receive bleomycin therapy for a variety of disorders are relatively young and may subsequently undergo surgery where general anaesthesia would be considered. Awareness and knowledge of these risk factors would certainly prove invaluable in preventing/avoiding perioperative complications in a patient with prior exposure to bleomycin. At this point, I would like to mention that the issue of perioperative reduction of oxygen in patients with prior exposure to bleomycin is also debatable.4, 5 There are conflicting reports regarding the role of pulmonary function tests and carbon monoxide diffusing capacity (DLco) as an indicator of bleomycin-induced pulmonary toxicity.6, 7 However, the general consensus is that DLco has an important role in this regard. As enquired by the reader, I would like to inform here that our patient did not receive any supplemental oxygen therapy after the administration of bleomycin. At the last review, which was approximately six months after stoppage of bleomycin, the individual was asymptomatic, a repeat pulmonary function test was normal. Repeat DLco test was done and was normal. After going through the existing literature and the pertinent comments of the reader, I think, it may be worthwhile to document in the medical records as well as personal health card and also brief the patient/care taker concerned on the recent exposure to bleomycin and possible potential complications if need arises for supplemental oxygen therapy or general anaesthesia for any reason in future. This may be particularly relevant for the Armed Forces population who move from place to place.

Supplemental oxygen therapy in bleomycin-induced pulmonary toxicity

Dear Editor, I read with interest the case report “Reversible Bleomycin Toxicity”.1 The authors have mentioned high-dose oxygen exposure as one of the risk factors for pulmonary toxicity. This is an important aspect of Bleomycin-induced pulmonary toxicity, as supplemental oxygen therapy is considered to be a synergistic toxin with Bleomycin, particularly in the setting of general anaesthesia and hyperbaric oxygen therapy (HBOT). The dosage of oxygen which can result in toxicity has not been quantified. Even a modest increase in fraction of inspired oxygen (FiO2) to 0.32 or 0.45, intra-operatively, has reportedly resulted in lung toxicity and death.2 Further, the duration of this relationship is not well characterised. An exposure to Bleomycin in the past six months is considered by some to be a significant risk factor;2 however for delivery of HBOT, even a remote history of Bleomycin therapy is an absolute contraindication.3 In patients with history of exposure to Bleomycin, requiring oxygen administration, inspired oxygen concentration is recommended to be kept at the lowest level, typically at FiO2 of 0.22–0.25, that provides adequate tissue oxygenation. A single breath, carbon monoxide diffusion capacity (DLco) is considered to be the most predictive of potential pulmonary toxicity where HBOT is being considered.4 The authors in their case report have not described if the patient received any supplemental oxygen therapy after the administration of Bleomycin. Also, they report that the initial pulmonary function test revealed moderate restrictive defect with impaired gas exchange, and the repeat pulmonary function test was normal. It has not been mentioned if DLco was performed and how significantly it improved after resolution of lung lesions. The finding of improved DLco may have a positive bearing if the patient subsequently requires supplemental oxygen therapy for any reason.

Pulmonary Function in Children with Sickle Cell Anemia Following Treatment with Hydroxyurea.

Background: Pulmonary function is particularly susceptible to acute and chronic injury occurring in patients with sickle cell anemia (SCA). Acute Chest Syndrome (ACS), a common and potentially fatal complication of SCA, can be the cause or the consequence of abnormal pulmonary function (Siddiqui & Ahmed, 2003). Use of hydroxyurea therapy (HU) is increasing for children with recurrent pulmonary complications, following the findings that HU reduces risk of ACS in adults (Charache et al, 1995). How HU may improve pulmonary function in children with SCA is still ill-defined. The purpose of this study was to assess the change observed on serial pulmonary function tests (PFT) for children prescribed HU for abnormal pulmonary function.Methods: Over 240 children with pulmonary complications, such as acute chest syndrome, reactive airway disease, and chronic hypoxia, have been evaluated in the Sickle Cell Pulmonary Clinic at Children's Healthcare of Atlanta since beginning in July 2000. As part of the Clinic's standard of care, PFT were routinely attempted on children over the age of 5. A retrospective review of PFT results was done for the children with SCA and prior abnormal PFT. Children were included in the HU cohort (+HU) if repeat PFTs were available following > 3 months on HU therapy and if time on HU did not include frequent RBC transfusions. Children without history of HU therapy (−HU) were selected for comparison. PFTs were performed on a standard plethysmograph. Paired t-test was used to evaluate observed differences.Results: Thirty-one children with prior abnormal PFT had test before and following prescription of HU. Their mean age was 12.6 (range 6–20) years and mean duration of HU was 21 (range 4–47) months at the time of the repeat PFT. Hematologic changes expected on HU occurred for all 31 children. Twenty-four children followed for abnormal PFT had no history of HU (−HU) and matched the +HU group by gender, age (mean 12.3, range 7–19 years), duration followed at time of repeat PFT (mean 19, range 3–66 months; p=0.36), and initial hematologic parameters. Spirometry findings changed for +HU group, and remained stable for −HU group. Mean FVC and FEV1 values improved significantly on HU, when compared to initial (PreHU) PFT and to −HU controls. Conversion to a normal PFT, as interpreted by a pediatric pulmonologist masked to treatment status, occurred in 18 (58%) and 2 (8%) children in the +HU and −HU groups, respectively.Table 1: Serial PFT and hematologic parameters according to HU exposure−HU (n=24)+HU (n=31)InitialRepeat#PreHURepeatPFT parameter1TLC88 (13.6)285 (11.7)85 (13.4)90 (13.5)FVC78 (9.8)79 (9.9)75 (12.6)90 (13.2)*,++FEV175 (9.6)74 (12.2)72 (11.4)86 (10.2)*,++FEF25-7575 (22)72 (28.0)77 (23.4)79 (26.8)FEV1/FVC (%)85(6.7)82 (9.8)87 (11.8)86 (11.1)Pulse oximetry (%)95 (3.1)96 (2.4)94 (4.4)97 (2.8)*WBC (x103/ul)14 (3.8)13 (2.9)13.02 (2.9)9.0 (2.1) *,++Hb (g/dl)8.0 (0.1)8.0 (0.9)7.8 (1.1)9.1 (1.3) *,++MCV (fl)84 (9.2)85 (10.0)87.3 (8.1)101.2 (10.1) *,++HbF (%)4.3 (1.5)5.2 (5.2)6.0 (3.8)14.0 (7.3) *,++1 % predicted value for age, sex and height of subject.2Mean (SD)#No significant changes compared to Initial, p > 0.05.*P value < 0.001 compared to PreHU;++P value < 0.001 compared to −HU repeat.Conclusions: Serial PFTs showed improved pulmonary function, following initiation of HU therapy in children with prior abnormal PFT. Routine PFT assessments of children prescribed HU may serve as an objective measure of clinical response in children with SCA and pulmonary complications. These results will help in the design of future prospective studies examining the clinical benefits of HU therapy for children at risk for long-term pulmonary complications.

The effect of education and training with balloons on pulmonary function test in children

Purpose : The results of pulmonary function test (PFT) in children are variable according to the patient's cooperation and comprehensiveness. This study has intended to figure out the effectiveness of pre-education and training with balloons on PFT in children. Methods : One hundred six children mean aged 9.35±2.92 years were tested. All participants performed PFT twice in 30 minutes intervals. First PFT were performed after usual instruction and second PFT were performed according to randomly classified grouping; Group 1 : repeat PFT after training with balloons, Group 2 : repeat PFT after training and education, both, Group 3 : repeat PFT after education about objects and necessities of pulmonary function test, Group 4 : repeat PFT without any education and training. Results : There were no difference statistically on the results of percent of predicted FEV1, FEV1/FVC, FEF25-75% and PEFR in Group 1, 2 and 4 patients. In some cases, the average is decreased with repeated PFT. At the case of repeated PFT after education, the average of percent of predicted FEV1, FEV1/FVC, FEF25-75% and PEFR is increased. There was statistically significant difference on the value of FEV1, FEF25-75% and PEFR between first and second PFT in Group 3. Conclusion : Training with balloons before PFT causes fatigueness and lowers concentration. Understanding of PFT makes results better than training. Therefore, enough explanation and education about PFT before examination is most effective for appropriate PFT in children.

Pulmonary Function in Uremic Patients on Long‐term Hemodialysis

Twenty patients with end‐stage renal failure who were on maintenance hemodialysis (HD) underwent pulmonary function testing (PFT) before and shortly after an HD session. On pre‐HD PFT, the mean values of all parameters except residual volume (RV) were in the normal range. Mean RV was high (152.9%), and mean diffusing capacity of the lung for carbon monoxide (DLCO) was high‐normal (110.4%). The pre‐HD static inspiratory (PImax) and expiratory pressures (PEmax) were much lower than normal (67.4% and 36.3%, respectively). After the HD session, repeat PFT revealed a small increase in expiratory flow rates, and a significant drop in PImax. There was a strong correlation between PImax and PEmax (r = 0.567, p < 0.01) at the pre‐ and post‐HD stages, indicating that common mechanism(s) are responsible for impairment of both inspiratory and expiratory muscle strength. The well‐preserved DLCO was thought to be due to the use of biocompatible dialyzer membranes. Chronic vascular congestion might be the other explanation of high DLCO.