Unsupervised Exercise in Interstitial Lung Disease: A Delphi Study to Develop a Consensus Preparticipation Screening Tool for Lymphangioleiomyomatosis.

BACKGROUND: Little research is available to provide practical guidance to health care providers for exercise preparticipation screening and referral of patients with interstitial lung diseases (ILD), including lymphangioleiomyomatosis (LAM), to participate in remote, unsupervised exercise programs. RESEARCH QUESTION: What exercise preparticipation screening steps are essential to determine whether a patient with LAM is medically appropriate to participate in a remote, unsupervised exercise program? STUDY DESIGN AND METHODS: Sixteen experts in LAM and ILD participated in a two-round modified Delphi study, ranking their level of agreement for ten statements related to unsupervised exercise training in LAM, with an a priori definition of consensus. Additionally, 60 patients with LAM completed a survey of the perceived risks and benefits of remote exercise training in LAM. RESULTS: Seven of the 10 statements reached consensus among experts. Experts agreed that an in-person clinical exercise test is indicated to screen for exercise-induced hypoxemia and prescribe supplemental oxygen therapy as indicated prior to initiating a remote exercise program. Patients with recent pneumothorax should wait to start an exercise program for at least 4 weeks until after resolution of pneumothorax and clearance by a physician. Patients with high cardiovascular risk for event during exercise, severe resting pulmonary hypertension, or risk for falls may be more appropriate for referral to a rehabilitation center. A LAM-specific remote exercise preparticipation screening tool was developed from the consensus statements and agreed upon by the panelists. INTERPRETATION: A modified Delphi study approach was useful to develop disease-specific recommendations for safety and preparticipation screening prior to unsupervised, remotely administered exercise in LAM. The primary product of this study is a clinical decision aid for providers to use when medically screening patients prior to participation in the newly launched LAMFit remote exercise program. FUNDING: This work was funded by an Established Investigator Award (LAM0130PB07-18) to MBB from The LAM Foundation.

Provider Perspectives on and Access to Palliative Care for Patients With Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) results in profound symptom burden and carries high mortality. Palliative care (PC) is dedicated to improving quality of life in patients with serious illness. Early PC provision improves rates of advance care planning and symptom management in patients with ILD. RESEARCH QUESTION: What are the current perspectives on PC among ILD providers, and what are the barriers to PC in ILD specialty centers? STUDY DESIGN AND METHODS: A 24-question electronic survey was disseminated to providers at the 68 Pulmonary Fibrosis Foundation Care Centers across the United States from October 2020 to December 2020. RESULTS: The survey was completed by 128 participants representing all 68 Pulmonary Fibrosis Foundation Care Center Network sites. Most respondents were physicians. Most providers exhibit good knowledge of, feel comfortable assessing a patient's readiness for, and agree with the need for PC for patients with ILD. Providers are most likely to refer to PC at objective disease and/or symptomatic progression rather than at initial diagnosis. In comparison with providers who report referring their patients to PC, providers who report rare referral are more likely to cite lack local PC availability (P < .01) and less likely to feel comfortable discussing prognosis/disease trajectory (P = .03) or feel it is important to address advance directives in ILD clinic (P = .02). There is a lack of standardized measures used to assess specific symptoms, overall symptom burden, or health-related quality of life across institutions. Discordance exists between self-reported and actual access to local inpatient and outpatient PC services. INTERPRETATION: Most ILD providers use PC and are comfortable discussing PC. Barriers to PC identified in this survey include the following: perceived lack of local access to PC, lack of systematic tools to assess symptom burden, lack of established optimal timing of PC referral, and unclear need for specialized PC delivery.

Rituximab Versus Cyclophosphamide for Central Nervous System Involvement of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Case Series.

OBJECTIVE: To compare the effectiveness of rituximab (RTX) with cyclophosphamide (CYC) in patients who have central nervous system (CNS) involvement in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: A computer-assisted search was conducted to identify all adults who received a diagnosis of AAV with CNS involvement from January 1, 1997, through July 1, 2017, at our institution. RESULTS: Of the 17 patients identified, 11 had received RTX, and 6 had received CYC. Age at diagnosis of CNS involvement was similar in both groups. In the RTX group, 91% of the patients were women; in the CYC group, 33% were women (p = 0.03). At the time of CNS presentation, orbital involvement had occurred in 6 patients in the RTX group and in none of the patients in the CYC group. Initial remission of induction was achieved in all patients (100%) in the CYC group and in 10 patients (91%) in the RTX group. Two patients had no response to RTX: 1 patient when RTX was used for remission induction at the time of diagnosis and the second patient when RTX was used for remission induction after relapse. The median follow-up was 38 months (range, 9-127 months). Central nervous system relapse occurred in 4 patients in the RTX group and in 1 patient in the CYC group. Of the 4 patients in the RTX group with relapse, 3 had marked ocular involvement. Both nonresponder patients in the RTX group had ocular involvement. CONCLUSION: Rituximab is as effective as CYC in remission induction in patients with CNS involvement in AAV.

Matrix metalloproteinase activity in the lung is increased in Hermansky-Pudlak syndrome.

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction and can sometimes lead to a highly aggressive form of pulmonary fibrosis that mimics the fatal lung condition called idiopathic pulmonary fibrosis (IPF). Although the activities of various matrix metalloproteinases (MMPs) are known to be dysregulated in IPF, it remains to be determined whether similar changes in these enzymes can be detected in HPS. RESULTS: Here, we show that transcript and protein levels as well as enzymatic activities of MMP-2 and -9 are markedly increased in the lungs of mice carrying the HPS Ap3b1 gene mutation. Moreover, immunohistochemical staining localized this increase in MMP expression to the distal pulmonary epithelium, and shRNA knockdown of the Ap3b1 gene in cultured lung epithelial cells resulted in a similar upregulation in MMP-2 and -9 expression. Mechanistically, we found that upregulation in MMP expression associated with increased activity of the serine/threonine kinase Akt, and pharmacological inhibition of this enzyme resulted in a dramatic suppression of MMP expression in Ap3b1 deficient lung epithelial cells. Similarly, levels and activity of different MMPs were also found to be increased in the lungs of mice carrying the Bloc3 HPS gene mutation and in the bronchoalveolar lavage fluid of subjects with HPS. However, an association between MMP activity and disease severity was not detected in these individuals. CONCLUSIONS: In summary, our findings indicate that MMP activity is dysregulated in the HPS lung, suggesting a role for these proteases as biological markers or pathogenic players in HPS lung disease.

Dental issues in lacrimo-auriculo-dento-digital syndrome: An autosomal dominant condition with clinical and genetic variability.

BACKGROUND AND OVERVIEW: Lacrimo-auriculo-dento-digital (LADD) syndrome is an autosomal dominant disorder with variable lacrimal and salivary gland hypoplasia and aplasia, auricular anomalies and hearing loss, dental defects and caries, and digital anomalies. CASE DESCRIPTION: The authors present the cases of 2 unrelated children with enamel defects and history of dry mouth leading to recurrent dental caries. The referring diagnoses were Sjögren disease and hypohidrotic ectodermal dysplasia, respectively. The geneticist suspected LADD syndrome, which was confirmed by means of molecular studies showing mutations of 2 genes: fibroblast growth factor receptor 2 and fibroblast growth factor 10, respectively. Similarly affected relatives indicated an autosomal dominant inheritance. These relatives needed multiple dental rehabilitations during childhood and dentures in adulthood. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Dry mouth, multiple caries, enamel defects, and abnormal tooth morphology were the reasons for seeking care from dentists. However, clinical evaluation and diagnostic imaging studies helped identify anomalies of the lacrimal and salivary glands, ears, and digits, indicating involvement of different areas of the body, compatible with LADD syndrome. Accordingly, dentists should consider genetic disorders in patients with multiple anomalies. For instance, oculodentodigital syndrome, oral-facial-digital syndrome, and LADD syndrome (among others) may have dental issues as the major clinical manifestation. Accurate identification of a particular syndrome is now commonplace with the use of genetic testing. When a patient has multiple anomalies suggestive of a syndromic condition, appropriate genetic testing can help verify the clinical diagnosis. Keeping genetics in mind helps earlier identification of other affected family members with diagnostic genetic testing and appropriate treatment; the economic advantage is to shorten the diagnostic odyssey and possibly preserve dentition.

Polyethylene glycol 3350 without electrolytes for the treatment of functional constipation in infants and toddlers.

OBJECTIVES: We have recently reported the safety and efficacy of polyethylene glycol 3350 without electrolytes (PEG) for the daily treatment of constipation in older children. Because there are very few data available on the use of PEG in infants and toddlers, we evaluated the efficacy and safety of PEG for the treatment of constipation in children <2 years of age. METHODS: This is a retrospective chart review of 75 constipated children <2 years of age at start of PEG therapy. PEG was started at an average dose of 1 g/kg body weight/d and parents were asked to adjust the dose to yield 1 to 2 soft painless stools/d. Data from the history and physical examination were collected initially and at short-term (or=6 months) follow-up. RESULTS: 75 otherwise healthy children received PEG for functional constipation. The mean age was 17 months (range, 1 to 24 months) and the mean duration of constipation was 10 months (range, 0.5 to 23 months). The mean duration of short-term follow-up was 2 months and mean duration of long-term follow-up was 11 months. The mean effective short-term PEG dose was 1.1 g/kg body weight/d and the mean long-term dose was 0.8 g/kg body weight/d. Constipation was relieved in 85% with short-term and in 91% with long-term PEG therapy. Adverse effects were mild and included diarrhea, which disappeared with lowering the dose. No subjects stopped PEG because of adverse effects. CONCLUSION: PEG is effective, well tolerated and appeared safe for the treatment of functional constipation in children <2 years of age.